Tag Archives: Life Science

Health Research off the Earth, For the Earth

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Today’s A Lab Aloft was posted by Ellen Stofan and Julie Robinson on April 17, 2015.

The International Space Station is a unique laboratory for performing investigations that affect human health both in space and on Earth. Since its assembly, the space station has supported research that is providing a better understanding of certain aspects of both fundamental and applied human health, such as the mechanisms causing aging and disease. Several biological and human physiological investigations have yielded important results, including improved understanding of bone loss and rebuilding, and development of new medical technologies that have impacted lives right here on Earth.

From studying the behavior of cells to developing potential improvements in clinical settings, a variety of health research arrived at the space station today aboard the sixth SpaceX contracted resupply mission. The Dragon spacecraft delivered research equipment for biology, biotechnology, human research, as well as additional research and supplies to the station. These new and ongoing investigations continue to assist researchers in pursuing scientific and medical knowledge not possible under the weight of gravity on Earth.

A SpaceX Falcon 9 rocket lifts off from Space Launch Complex 40 at Cape Canaveral Air Force Station carrying the Dragon resupply spacecraft on the sixth commercial resupply services mission to the International Space Station. Liftoff was at 4:10 p.m. EDT on April 14. (NASA/Tony Gray)

A SpaceX Falcon 9 rocket lifts off from Space Launch Complex 40 at Cape Canaveral Air Force Station carrying the Dragon resupply spacecraft on the sixth commercial resupply services mission to the International Space Station. Liftoff was at 4:10 p.m. EDT on April 14. (NASA/Tony Gray)

NASA astronaut Scott Kelly and his identical twin brother Mark will participate in a series of human health studies as part of the recently begun One-Year Mission aboard the space station. The data collected comparing the twins, Scott on the space station, and Mark living on Earth, will enable researchers to determine how cognitive function, metabolic profiles, gastrointestinal microbiota, immune system and genetic sequences are affected by different factors attributable to the environmental stress of spaceflight. Results could potentially be used as the first steps to understand how to help develop new treatments and preventive measures for health issues on Earth.

Another investigation will study how and why some astronauts experience eye changes that can affect their vision during missions aboard the station. There are several factors that may cause this problem during spaceflight. This research will improve scientists’ understanding of this phenomenon and how changes in the brain and eye shape affects vision. It could also help people on Earth suffering from conditions that increase swelling and pressure in the brain.

NASA astronaut Michael Hopkins and European Space Agency astronaut Luca Parmitano perform ultrasound eye imaging as part of the Fluid Shifts investigation during Expedition 37 on the International Space Station. (NASA)

NASA astronaut Michael Hopkins and European Space Agency astronaut Luca Parmitano perform ultrasound eye imaging as part of the Fluid Shifts investigation during Expedition 37 on the International Space Station. (NASA)

Studying cells in space is another important area of health research on the station. Research in microgravity provides an important novel tool to better understand the mechanisms that cause cellular functions such as cell division, gene expression and shape. Looking at cells in space provides unique insights, because in the absence of Earth’s gravity, cells grow with a similar structure as they do in the body. Scientists can use this knowledge to improve diagnosis and therapies.

A type of bone cell, called osteocytes, will arrive at the space station on today’s cargo delivery as part of a project funded under the Biomedical Research on the International Space Station (BioMed-ISS). This initiative is a collaborative effort among the National Institutes of Health, the ISS National Laboratory and NASA. The investigation team, led by Dr. Paola Divieti Pajevic, Assistant Professor at Boston University and the Director of the bone cell core at Massachusetts General Hospital, will analyze the effects of microgravity on the function of osteocytes. The study will provide better understanding of the mechanisms behind bone disorders on Earth, such as osteoporosis.

The three colorful bioreactors where mouse bone cells grow within a 3D material for the Osteo-4 investigation aboard the International Space Station. (Divieti Pajevic Laboratory)

The three colorful bioreactors where mouse bone cells grow within a 3D material for the Osteo-4 investigation aboard the International Space Station. (Divieti Pajevic Laboratory)

Additional investigations also may yield results that can potentially improve patient health in clinical settings on Earth. Scientists may be able to develop methods for combating hospital-acquired infections, a chronic problem in clinical settings, by researching bacterial growth in a microgravity environment. Moreover, by studying protein crystallization in space, scientists may be able to improve crystallization technology that can change the way drugs are used for treating various human diseases.

The programs outlined here illustrate only a fraction of the space station’s potential as a groundbreaking scientific research facility. The International Space Station National Laboratory, as designated by the 2005 NASA Authorization Act, is a unique scientific platform that continues to enable researchers to put their talents to work on innovative experiments that could not be done anywhere else. Use of the space station’s singular capabilities as a permanent microgravity platform with exposure to the space environment is improving life on Earth; fostering relationships among NASA, other federal entities, and the private sector; and advancing science, technology, engineering and mathematics (STEM) education.

We may not know yet what will be the most important discovery gained from this orbiting laboratory, but we already are doing significant research on the International Space Station that could greatly benefit human health. Through advancing the state of scientific knowledge of our planet, looking after our health, and providing a space platform that inspires and educates health, science and technology leaders of tomorrow, these benefits will drive the legacy of the space station as its research enhances the quality of life here on Earth.

Ellen Stofan is the Chief Scientist for the National Aeronautics and Space Administration (NASA/Jay Westcott)

Ellen Stofan is the Chief Scientist for the National Aeronautics and Space Administration (NASA/Jay Westcott)

NASA’s International Space Station Chief Scientist Julie Robinson, Ph.D. (NASA)

 

 

Women in Space Part Two, What’s Gender Got To Do With It?

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In today’s A Lab Aloft, guest blogger Liz Warren, Ph.D., looks at the differences between male and female astronaut physiology on long duration space missions.

I hate to break it to you, but men are not actually from Mars and women are not really from Venus. This silly saying illustrates a question that researchers, however, are serious about studying. With International Women’s Day around the corner, I thought it the ideal time to address the question: Is there a difference between the sexes as the human body adapts to microgravity?

You may remember reading the earlier blog that I wrote about celebrating “firsts” for women space explorers. The sky is certainly no longer the limit for females interested in exploration, science or any other career they wish to pursue. In fact, if you’re following our current mission, you already know we have two women living and working on the International Space Station.

ESA astronaut Samantha Cristoforetti and Roscosmos cosmonaut Yelena Serova live and work aboard the International Space Station as part of the current crew. (NASA)

Roscosmos cosmonaut Yelena Serova and ESA astronaut Samantha Cristoforetti live and work aboard the International Space Station as part of the current crew. (NASA)

In the fall of 2015, Sarah Brightman will be the 60th woman to fly in space. As we approach longer durations in human spaceflight, such as the one-year mission and the journey to Mars, it is important to tease out all aspects of how humans handle life in microgravity to ensure crew safety. The answers may also hold insights for human health even if you never leave the ground.

Our current crew aboard the space station includes ESA (European Space Agency) astronaut of Italian nationality, Samantha Cristoforetti, and a Roscosmos cosmonaut of Russian nationality, Yelena Serova. While serving aboard the orbiting laboratory for about six months, they each perform experiments in disciplines that range from technology development, physical sciences, human research, biology and biotechnology to Earth observations. This research helps in benefitting our lives here on Earth and enables future space exploration. They also engage students through educational activities in addition to operational tasks such as equipment maintenance and visiting vehicle tasks.

Russian cosmonaut Elena Serova, Expedition 41 flight engineer, works with hardware for the ОБР-8 Khimiya-Obrazovanie (Chemistry-Education) experiment in the Glove Minibox. Image was taken in the Rassvet Mini-Research Module 1 (MRM1) of the International Space Station. (NASA)

Russian cosmonaut Elena Serova, Expedition 41 flight engineer, works with hardware for the ОБР-8 Khimiya-Obrazovanie (Chemistry-Education) experiment in the Glove Minibox. Image was taken in the Rassvet Mini-Research Module 1 (MRM1) of the International Space Station. (NASA)

It’s important to acknowledge the contributions women in space make to both exploration and research. For instance, on Feb. 3, a prestigious tribute went to another woman space explorer, Japan Aerospace Exploration Agency (JAXA) astronaut Chiaki Mukai. She was conferred the National Order of the Legion of Honour, Chevalier. Mukai flew aboard space shuttle missions STS-65 and STS-95, and is currently the director of the JAXA Center for Applied Space Medicine and Human Research (J-CASMHR). The work these trailblazers accomplish also includes their role as research subjects themselves.

Female space explorers are skilled professionals, representing the best humanity has to offer, executing complex tasks in an unforgiving environment. Their sex differentiates them only so far as biology determines—which is exactly the topic covered in a recent compendium titled “Impact of Sex and Gender on Adaptation to Space.” The results were published in the November 2014 issue of the Journal of Women’s Health.

Samantha Cristoforetti taking images of the Earth from the International Space Station’s cupola. (NASA)

Samantha Cristoforetti taking images of the Earth from the International Space Station’s cupola. (NASA)

Space exploration is inherently dangerous, and as we look to longer duration spaceflights to Mars and beyond, NASA wants to make sure we are addressing the right questions to minimize risk to our astronaut crews. Based on a recommendation by the National Academy of Sciences, NASA and the National Space Biomedical Research Institute (NSBRI) assembled six scientific working groups to compile and summarize the current body of knowledge about the different ways that spaceflight affects the bodies of men and women. The groups focused on cardiovascular, immunological, sensorimotor, musculoskeletal, reproductive and behavioral implications on spaceflight adaptation for men and women. NASA and NSBRI created a diagram summarizing differences between men and women in cardiovascular, immunologic, sensorimotor, musculoskeletal, and behavioral adaptations to human spaceflight.

Thus far, the differences between the male and female adaptation to spaceflight are not significant. In other words, mission managers planning a trip to Mars, for example, can do so without consideration of the sex of the crew members. However, many questions remain unanswered and require further studies and more women subjects in the human-health investigations. There is an imbalance in data available for men and women, primarily due to fewer women having flown in space.

As a physiologist, I am intrigued by several of the differences described in the journal. An area that interests me in particular is cardiovascular physiology. According to the Centers for Disease Control and Prevention, cardiovascular disease—including heart disease, stroke and high blood pressure—is the number one killer of men and women across America. Many studies have shown that healthy habits including good nutrition and exercise are important for maintaining a healthy heart here on Earth. Those habits are even more important for astronauts on the space station.

Of the findings described in the journal, one is that women astronauts tend to suffer more orthostatic intolerance upon standing after return to Earth. Related to this finding, women also appear to lose more blood plasma during spaceflight. Possibly connected to the inherent differences in the cardiovascular system between men and women, male astronauts appear to suffer more vision impairment issues in space than women, although the difference is not statistically significant due to the small number of subjects—meaning more research needs to be done.

NASA astronaut Karen Nyberg, Expedition 36 flight engineer, conducts an ocular health exam on herself in the Destiny laboratory of the Earth-orbiting International Space Station. (NASA)

NASA astronaut Karen Nyberg, Expedition 36 flight engineer, conducts an ocular health exam on herself in the Destiny laboratory of the Earth-orbiting International Space Station. (NASA)

Another difference between men and women in spaceflight is worth noting, and that is the radiation standard. While the level of risk allowed for both men and women in space is the same, women have a lower threshold for space radiation exposure than men, according to our models.

This is an exciting time in human space exploration. We are addressing questions today that will lead to safer journeys off our planet. This month, NASA astronaut Scott Kelly and Russian cosmonaut Mikhail Kornienko will embark on the first joint U.S.-Russian one-year mission to the space station. Most stays on station are six months in duration, but planners anticipate a journey to Mars to be closer to 1,000 days. This first one-year mission is a stepping stone in our travels beyond low-Earth orbit. NASA anticipates to continue one-year long missions, and women will be part of these crew selections.

NASA astronaut Scott Kelly (left), Expedition 43/44 flight engineer and Expedition 45/46 commander; and Russian cosmonaut Mikhail Kornienko, Expedition 43-46 flight engineer, take a break from training at NASA’s Johnson Space Center in Houston to pose for a portrait. (NASA)

NASA astronaut Scott Kelly (left), Expedition 43/44 flight engineer and Expedition 45/46 commander; and Russian cosmonaut Mikhail Kornienko, Expedition 43-46 flight engineer, take a break from training at NASA’s Johnson Space Center in Houston to pose for a portrait. (NASA)

In the meantime, what we learn about our bodies off the Earth has benefits for the Earth. In part one of this guest blog, I stated that, “in space exploration and in science, we stand on the shoulders of those who came before us.” I am thrilled to think of what we are about to learn from the one-year mission, as well as the continued research on and by both men and women in orbit. What an exciting time for humanity!

Liz Warren, Ph.D., communications strategist for the International Space Station Program Science Office. (NASA)

Liz Warren, Ph.D., communications strategist for the International Space Station Program Science Office. (NASA)

Liz Warren, Ph.D., is a physiologist with Barrios Technology, a NASA contractor supporting the International Space Station Program Science Office. Warren has a doctorate in molecular, cellular, and integrative physiology from the University of California at Davis, completed post-doctoral fellowships in molecular and cell biology and neuroscience, and has authored publications ranging from artificial gravity protocols to neuroscience to energy balance and metabolism.

Rodent Research Ramps Up Aboard the International Space Station

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In today’s A Lab Aloft International Space Station Assistant Program Scientist Kirt Costello, Ph.D., lays out what’s new in rodent research in orbit. The updated facility and planned studies will advance capabilities for microgravity life science and biology research.

In this blog we often talk about the “why” reasons for the research that we are doing on the International Space Station, but sometimes it’s also important to talk about “where” NASA gets the ideas. Specifically, where do the concepts and research announcements come from? How does NASA know that the science being selected fits the needs of the country in its quest to get the most beneficial use of the space station’s national laboratory?

Today’s discussion is on the new space station Rodent Research Facility and the objectives that NASA is trying to meet by making this system available to both researchers seeking safe exploration of space and those seeking improvements in health here on Earth. Many of these investigations directed specifically at improving life on Earth come through the Center for the Advancement of Science in Space (CASIS) as the manager of the space station’s national laboratory resources.

Image of the Mouse Immunology (MI) Animal Enclosure Modules (AEM). (NASA)

Image of the Mouse Immunology (MI) Animal Enclosure Modules (AEM). (NASA)

NASA has been conducting rodent research in space for many years. The majority of those investigations focus on clinical questions about how we keep our astronauts healthy in space for longer periods. They also address very basic life science questions about how animal physiology changes in a weightless environment. Prior to and during the time of station assembly, the Space Shuttle Program hosted the Animal Enclosure Module (AEM) studies. The AEM flew 28 missions conducting research, such as the Commercial Biomedical Testing Module or CBTM investigations. The AEM system was well suited to the Space Transportation System (STS), allowing researchers important access to their rodent subjects both before flight and during post flight recovery.

With the end of the shuttle program, it was clear that the use of newly designed transportation vehicles would necessitate redesign efforts for AEM use aboard station. Conducting such investigations not on the vehicle, but aboard the station would enable longer-duration studies. The change from a few weeks to a few months in microgravity increases the potential research returns, but also requires some changes in the design of the hardware.

NASA’s Rodent Habitat module, seen here with both access doors open, is the next generation replacement to its predecessor, the Animal Enclosure Module (AEM). (NASA/Dominic Hart)

NASA’s Rodent Habitat module, seen here with both access doors open, is the next generation replacement to its predecessor, the Animal Enclosure Module (AEM). (NASA/Dominic Hart)

The importance of continuing rodent research aboard the space station is laid out by the National Research Council (NRC) in their 2010 Decadal Study Report, “Recapturing a Future for Space Exploration Life and Physical Sciences Research for a new Era.” In that study’s section on animal and human biology a third of the recommendations specifically called out the use of mouse or animal model organisms as the mechanism to proceed with research on the orbiting laboratory. These recommendations focus on muscle and bone loss, the testing of drugs for osteoporosis, changes to the animal immune system, the effects of aerosol exposures to the lungs and multi-generational and developmental studies.

To accomplish the wide array of research that the NRC proposed, some improvements were made to the AEM system to update the workhorse that had served well during the shuttle years. Improvements include features such as upgraded longer lasting filters, changeable food trays and support systems within the microgravity science glovebox (MSG) facility. These changes allow for studies to focus on the effects of microgravity exposure over much longer time frames. While the AEM of the shuttle era only housed rodents for up to 17 days, the new facility on space station can maintain an investigation for months.

NASA astronaut Nicole P. Stott, STS-133 mission specialist, is photographed using a camcorder to record Mouse Immunology-2 investigation in one of the orbiter Discovery’s middeck lockers. (NASA)

NASA astronaut Nicole P. Stott, STS-133 mission specialist, is photographed using a camcorder to record Mouse Immunology-2 investigation in one of the orbiter Discovery’s middeck lockers. (NASA)

Part of what makes rodents ideal test subjects is the fact that they reach maturity and age much quicker than humans. The typical rodent lifetime is about 2.5 years versus about 72 years for the comparable human. The capability to support rodents for up to 180 day stays is in development for the space station. During stays that long, researchers can begin to investigate questions that deal with developmental biology and extended exposure to microgravity. A half a year stay for a rodent might be the equivalent of a 14 year exposure to a human.

Updates to the old system also add both white light and infrared cameras for observing rodent conditions and behaviors. This capability allows researchers on the ground to closely monitor their studies. It also requires less crew time, as the observations can be done remotely, which in turn frees up that crew time to get more science done aboard the space station.

The first flight of the new Rodent Research Facility is on the upcoming SpaceX-4 mission to the space station. During this flight, designers will validate all of the initial performance goals for the rodent research hardware. The facility also will get a head start on some of the NRC decadal recommended goals with the CASIS sponsored portion of the Rodent Research-1 investigation. This study will include 10 of the 20 mice flying in the two habitats, and is in partnership with the commercial pharmaceutical company, Novartis.

A view of the SpaceX Dragon Commercial Resupply Services-3 (CRS-3) spacecraft grappled by the Canadarm2 Space Station Remote Manipulator System (SSRMS) during Expedition 39. (NASA)

A view of the SpaceX Dragon Commercial Resupply Services-3 (CRS-3) spacecraft grappled by the Canadarm2 Space Station Remote Manipulator System (SSRMS) during Expedition 39. (NASA)

The test subjects will live aboard the space station for about 21 days. The CASIS mice will include five wild type—or typical—and five transgenic MuRF-1 knockout mice. Researchers will compare results from these two groups and the ground control counterparts to determine whether this genetic knockout impacts muscle atrophy and muscle sparing—where tissue is conserved—in those mice.

While the inaugural flight of the new rodent habitat system is right around the bend, the rodent research project team at NASA’s Ames Research Center is already hard at work. They are planning more complex investigations and improving the system to accommodate longer durations and more experimental aims for researchers. Rodent research will become a routine part of space station for the decade to come.

For me, personally, it’s been a great experience working with these teams to get this facility ready for flight. I’m excited by all the possibilities for the new research avenues that this opens for NASA and CASIS researchers. I’m humbled by the effort that has gone into this capability, and I hope you all will tune in during the mission to follow along with the accomplishments of the team.

Kirt Costello completed a Ph.D. in Space Physics and Astronomy at Rice University in 1998. Kirt is the Assistant International Space Station Program Scientist for National Research. In this position he works with the International Space Station Chief Scientist, NASA research organizations and CASIS to advise on the objectives and priorities of science being prepared to fly to the space station.

A PECASE for Space and Skeletal Biology Research

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In today’s A Lab Aloft, Joshua S. Alwood, Ph.D., shares his postdoctoral research into the impact of microgravity and ionizing radiation exposure on bone health – work that led to his receiving the 2012 Presidential Early Career Award for Scientists and Engineers.

I am honored to be a recipient of a 2012 Presidential Early Career Award for Scientists and Engineers (PECASE). This award is based on the cumulative body of work achieved during my postdoctoral fellowship at NASA’s Ames Research Center in Moffett Field, Calif., while working with my advisor Ruth Globus, Ph.D. and on my contribution to experiments that flew on International Space Station assembly flights STS-131 and STS-135 with collaborator Eduardo Almeida, Ph.D.

Ellen Stofan, Ph.D., NASA's Chief Scientist presents Josh Alwood, Ph.D., the 2012 Presidential Early Career Award for Scientists and Engineers (PECASE) award. (NASA/Joel Kowsky)

Ellen Stofan, Ph.D., NASA’s chief scientist presents Josh Alwood, Ph.D., the 2012 Presidential Early Career Award for Scientists and Engineers (PECASE) award. (NASA/Joel Kowsky)

The big question motivating our studies is, how does spaceflight cause bone loss in astronauts? While weightless, astronauts lose about one percent bone mineral density per month. To put this into context, this is about 10 times faster than osteoporosis typically progresses on Earth. The longer the mission, particularly outside Earth’s protective magnetic fields, the greater the doses of ionizing radiation astronauts will accumulate, which may also negatively impact the skeleton.

NASA astronauts Tracy Caldwell, STS-118 mission specialist, and Charles Hobaugh, pilot, working with the Commercial Biomedical Testing Module 2 investigation aboard space shuttle Endeavour. (NASA)

NASA astronauts Tracy Caldwell, STS-118 mission specialist, and Charles Hobaugh, pilot, working with the Commercial Biomedical Testing Module 2 investigation aboard space shuttle Endeavour. (NASA)

In our ground-based research, we asked the following questions: how do the conditions of simulated weightlessness and ionizing radiation exposure affect the skeleton, and are the results any different when these conditions are combined? Our results suggest that each condition causes bone loss on its own, though at differing rates and severity. Together, weightlessness and radiation exposure cause bone loss to worsen beyond either treatment alone. These results have to do with the behavior of different types of bone cells. Combined, the balance of bone formation and bone resorption—breaking down—define a normal process called bone remodeling, which the body uses to maintain a healthy skeletal structure throughout life.

Following radiation exposure, there is a rapid stimulation of bone resorption—this can lead to a net loss of skeletal tissue caused by a specific cell called an osteoclast. We quantify this by measuring the number of osteoclast cells on the surface on the bone and their level of activity through specific proteins secreted into circulation. At the tissue level, we use X-ray imaging and computed tomography to build and quantify three-dimensional models of the skeleton. This rapid resorption is concentrated, yet it appears to be short-lived. At the doses we’ve investigated, it doesn’t get worse after the initial burst.

X-rays of mouse bones from the CBTM study showing a ground control (left), as treated with Osteoprotegerin in microgravity (middle), and with no drug treatment during spaceflight (right). (L. Stodieck, Bioserve and T. Bateman, University of North Carolina)

X-rays of mouse bones from the Commercial Biomedical Testing Module (CBTM) study showing a ground control (left), as treated with Osteoprotegerin in microgravity (middle), and with no drug treatment during spaceflight (right). (L. Stodieck, Bioserve and T. Bateman, University of North Carolina)

In contrast, structural changes caused by simulated weightlessness gradually appear. Simulated weightlessness activates bone resorption by the osteoclasts and additionally reduces bone formation by inhibiting a second cell type called an osteoblast.

Exposure to space radiation affects osteoblasts as well. Our research shows that at the estimated doses potentially accumulated over a three-year Mars mission, long-lasting effects to the osteoblast-lineage cells occur. This may result in abnormal bone remodeling in the long-term. To this end, we determined that spongy bone—found on the inside of some bones—recovered less efficiently following radiation exposure vs. recovery from simulated microgravity.

Osteocyte lacunae from the ground-based control (left) and after 15 days of spaceflight (right). Space-flown lacunae appear larger, indicative of osteocytic remodeling. (Blaber, et al, PLoS One, 2013)

Osteocyte lacunae from the ground-based control (left) and after 15 days of spaceflight (right). Space-flown lacunae appear larger, indicative of osteocytic remodeling. (Blaber, et al, PLoS One, 2013)

The second component of the PECASE acknowledges my work with the Biospecimen Sharing Program for shuttle flight STS-131. Along with Almeida, the project investigator, I used a new application of a high-resolution (30 nanometer) X-ray transmission microscope at the SLAC National Accelerator Laboratory to analyze bone health following 15 days of spaceflight.

We scanned the bones and processed the images for three-dimensional tomographic analyses. As a result, we were able to quantify changes in the bone’s osteocyte cells. In a unique mechanism of bone loss, osteocytes actively remodel and enlarge their living spaces, known as lacunae, in response to spaceflight. This is an additional mode of bone resorption that occurs during spaceflight at the bone’s surface.

My research employs a basic biology approach with the overriding motivation to enable human exploration of space. In other words, the goal is to expand the envelope of mission durations, the distance from Earth that missions can access, and to mitigate the skeletal consequences following radiation exposure for astronauts. My colleagues and I use a basic approach to uncover the cellular and molecular mechanisms that underlie skeletal changes in the space environment. Eventually we can use this knowledge to develop countermeasures to better manage astronaut skeletal health.

On Earth, this research has applications towards improving our knowledge of bone diseases such as osteoporosis. It may also help people living sedentary lifestyles, providing positive impacts to their health. The sedentary environment is somewhat similar to weightlessness. The take-home message: use your skeleton or lose it. The ability to work on advancing an area of biology that may help humans both in space and on the ground is truly its own reward.

Fluorescent image of femur diaphysis from ground control placebo treated mouse, indicating greatly decreased bone formation. (NASA)

Fluorescent image of femur diaphysis from ground control placebo treated mouse, indicating greatly decreased bone formation. (NASA)

I was inspired to enter this area of research from childhood experiences. I grew up in Florida and witnessed space shuttle launches in my front yard. This really captivated my attention towards space. As I got older, I learned about the skeleton and how it is a living structure that adapts to its mechanical environment. For example, joggers experience forces equivalent to about three times their body weight. Those two factors overlapped in my extracurricular readings on astronauts and the changes in their bodies during weightlessness. That connection propelled me to focus on science and engineering in my education, and further to study the skeleton. I am driven to continually learn new things, which prompted me to enter graduate school and become an independent researcher.

NASA astronaut Nicole Stott, STS-133 mission specialist, using a camcorder to record Mouse Immunology-2 investigation in one of the space shuttle Discovery’s middeck lockers. (NASA)

NASA astronaut Nicole Stott, STS-133 mission specialist, using a camcorder to record Mouse Immunology-2 investigation in one of the space shuttle Discovery’s middeck lockers. (NASA)

Although I do not have an immediate investigation going to the space station, I am applying for opportunities through NASA’s Space Biology Project. It’s an exciting time to be part of NASA’s research program. In the meantime, I continue to develop hypotheses worth studying aboard the space station and generating preliminary evidence while working in my lab on the ground. My goal is to eventually take my science into orbit or beyond.

The work cited in this PECASE Award was made possible by key funding organizations, including NASA Space Biology; grants to Globus from the National Space Biomedicine Research Institute; the U.S. Department of Energy and the NASA Space Radiation Project Element; and grants to Almeida from the NASA Bion-M1 Biospecimen Sharing Program and the National Institutes of Health / National Institute of Biomedical Imaging and Bioengineering.

Josh Alwood in the Bone and Signaling Lab at NASA's Ames Research Center. (NASA /Dominic Hart)

Josh Alwood in the Bone and Signaling Laboratory at NASA’s Ames Research Center in Moffett Field, Calif. (NASA /Dominic Hart)

Joshua S. Alwood, Ph.D., is a senior scientist with CSS-Dynamac working at the Bone and Signaling Lab at NASA’s Ames Research Center in Moffett Field, Calif. Alwood earned his Ph.D. in Aeronautics and Astronautics from Stanford University, as well B.S. degrees in Physics and Astronomy from the University of Florida.

Crystallizing Opportunities With Space Station Research

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In today’s A Lab Aloft, Dr. Larry DeLucas, a primary investigator for International Space Station studies on protein crystal growth in microgravity, explains the importance of such investigations and how they can lead to human health benefits.

We have many proteins in our body, but nobody knows just how many. Consider that the human genome project is more than 20,000 protein-coding genes, and many of these genes or portions of those genes combine with others to create new proteins. The human body could have anywhere from a half million to as many as two million proteins—we’re not sure. What we do know, is that these proteins control aspects of human health and understanding them is an important beginning step in developing and improving treatments for diseases and much more.

A protein crystal is a specific protein repeated over and over a hundred thousand times or more in a perfect lattice. Like a row of bricks on a wall, but in three dimensions. The more perfectly aligned that row of bricks or the protein in the crystal, the more we can learn of its nature. Today there are more than 50,000 proteins that have been crystallized and the structures of the three-dimensional proteins comprising these crystals have been determined. Unfortunately many important proteins that we would like to know the three-dimensional structures for have either resisted crystallization or have yielded crystals of such inferior quality that their structures cannot be determined.

Crystals of insulin grown in space (left) helped scientists determine the vital enzyme's structure with much higher resolution than possible with Earth-grown crystals (right). (NASA)

Crystals of insulin grown in space (left) helped scientists determine the vital enzyme’s structure with much higher resolution than possible with Earth-grown crystals (right). (NASA)

Once we have a usable protein crystal—one that is large and perfect enough to examine—the primary technique we use to determine the protein molecular structures is x-ray crystallography. When we expose protein crystals to an x-ray beam, we get what’s called constructive interference. This is where the diffracted x-rays coming from the electrons around each atom and each protein come together, providing a more intense diffraction spot. We collect hundreds of thousands, sometimes millions of diffraction spots for a protein. The more perfectly ordered the individual protein molecules are within the crystals, the more intense these spots. The higher signal to noise ratio in these strong spots creates an improved resolution of the structure, allowing us to map the crystal in detail.

Well-ordered protein crystal x-ray diffractions create sharp patterns of scattered light on film. Researchers can use a computer to generate a model of a protein molecule using patterns like this. (NASA)

Well-ordered protein crystal x-ray diffractions create sharp patterns of scattered light on film. Researchers can use a computer to generate a model of a protein molecule using patterns like this. (NASA)

Using computers, we take those diffraction spots and mathematically determine the structure of where every atom is in the protein. For example, in most protein structures we can’t even see the hydrogen atoms. We guess where they are because we know the length of a hydrogen bond. So if we see a nitrogen atom from an amino acid that we know has a hydrogen linked to it, and then at a hydrogen-bonding distance away we see an oxygen atom, then we can make an educated guess that the hydrogen is pointed towards that oxygen atom, so we position it there.

While we can grow high-resolution crystals both in space and on the ground, those grown in space are often more perfectly formed. That’s the main advantage and reason we’ve gone to space for these studies. In many cases where we could not see hydrogen crystals on the ground, we then flew that protein crystal in space and let them grow in microgravity. Because of the resulting improved order of the molecules laying down in the crystal lattice, we were able to actually see the hydrogen atoms. Usually to see the hydrogen atoms, you are talking about getting down to a resolution of one angstrom, which is not easy to do—it would take 10 million angstroms to equal one millimeter!

Another example of protein crystals grown in space (right), which are larger and more perfect than those grown on the ground (left). (JAXA)

Another example of protein crystals grown in space (right), which are larger and more perfect than those grown on the ground (left). (JAXA)

We also can look at bacteria and virus protein structures to identify how to target those proteins with drugs. Having this information is very important to pharmaceutical companies and universities. That structure provides a road map that is critical for the understanding of the life cycle of the bacteria or virus.

We’ve only done a fraction of the more important complex protein structures–I’m referring to membrane proteins and protein-protein complexes. Protein complexes are often composed of two, three or more proteins that interact together to form new macromolecular complexes that are often important in terms of disease and drug development. Membrane proteins are the targets for about 55 percent of the drugs on the market today. Scientists have determined the three-dimensional structures for less than 300 membrane protein structures thus far. However, there remain thousands more for which the structures would help scientists understand their important roles in chronic and infectious diseases.

When we see a specific region in a protein and we know exactly where every atom is, chemists can design drugs that will interact in those regions. We can take some of the drugs they design that work, but maybe not as well as we would like. We then grow new crystals of the protein with the drug attached to the protein to see exactly how it’s bound to the protein. That lets other scientists—modelers—determine very clearly how the drug interacts with the protein, information that enables them to design new, more effective compounds. This whole process is called structure-based drug design.

The International Space Station provides a unique environment where we can improve the quality of protein crystals. During the days of protein crystallization studies on the space shuttle, one of the most frustrating aspects of the microgravity experiments was the length of time it took to produce a usable crystal. This is actually part of why space-developed crystals are better—they grow much more slowly. On the shuttle you only had 10-12 days for a study, but aboard the space station you have as long as you need.

As an astronaut and scientist, I personally flew a record 14-day flight in 1992 where we studied 31 proteins. I was looking at results and planning to set up new experiments, changing the chemical conditions to optimize the crystallization. The rule for my sample selection was that the proteins had to nucleate—that means to begin to grow a crystal—and grow to full size in three days. Once I got up there, however, by the third day nothing had nucleated. I was worried, but then on the fourth day I could see little sparkles where crystals had started to grow in about half of the proteins. By mission end I was really only able to optimize the crystal growth for six of the proteins. How much longer it takes a crystal to nucleate and grow to full size was a dramatic discovery.

Astronaut Larry DeLucas, payload specialist, handles a Protein Crystal Growth (PCG) sample at the multipurpose glovebox aboard the Earth-orbiting space shuttle Columbia. (NASA)

Astronaut Larry DeLucas, payload specialist, handles a Protein Crystal Growth (PCG) sample at the multipurpose glovebox aboard the Earth-orbiting space shuttle Columbia. (NASA)

With constant access to a microgravity lab, such as the space station, I am confident that we can improve the quality of any crystal. With protein crystals it is important to note that just because we get a better structure with higher resolution, it doesn’t at all mean it’s going to lead to a drug.

The ability to grow good crystals typically involves a great deal of preparation on the ground where we first express and purify and grow the initial crystals. But if space can give you higher resolution, there’s no drug discovery program that’s going to take a lower resolution option. From the time you determine that structure and chemists work with it, the typical time frame to develop a drug is 15 to 20 years and the cost is around a billion dollars. Identifying the structure of the protein crystal is only the first step. Many times even with the structure a project goes nowhere because the drugs they develop end up being unusable. There are so many aspects to drug discovery beyond the opening act of structure mapping.

If crystals and the structure of a target protein are available, pharmaceutical and biotech companies certainly prefer to use that structure to help guide the drug discovery. After the first 18 months they’ve developed the drug candidates, they may not need to use the crystal structure again for say 10 years. During that time they are doing clinical trials and pharmacology. The majority of the money it takes to get a drug approved by the FDA is after the initial phase. If you break down what they say is about a billion dollars to develop a drug, the portion needed to get the structure up front will range from half to two million dollars—a small fraction of the whole process.

View of Expedition 28 Flight Engineer Satoshi Furukawa with the JAXA Protein Crystal Growth (PCG) investigation aboard the International Space Station Japanese Experiment Module (JEM). (NASA)

View of Expedition 28 Flight Engineer Satoshi Furukawa with the JAXA Protein Crystal Growth (PCG) investigation aboard the International Space Station Japanese Experiment Module (JEM). (NASA)

For the upcoming Comprehensive Evaluation of Microgravity Protein Crystallization investigation we focused on two things. First, we selected proteins that are of high value based on their biology. Having this information of their structure can lead to new information about structural biology—how proteins work in our body. The other major requirement for the candidates for selection was that the proteins had to have already been crystallized on Earth, but the Earth-grown crystals were not of good quality.

We are flying 100 proteins to the space station on SpaceX-3, currently scheduled for March 2014. Twenty-two of these are membrane proteins, 12 are protein complexes, and the rest are aqueous proteins important for the biology we will learn from their structures. The associated disease was the last thing we considered, as we were looking at the bigger picture of the biology. That being said, for the upcoming proteins flying you can almost name a disease: cystic fibrosis, diabetes; several types of cancer, including colon and prostate; many antibacterial proteins; antifungals; etc. There are even some involved with understanding how cells produce energy, which I suspect could lead to a better understanding of molecular energy.

Not long ago a Nobel Prize was awarded for the mapping of the ribosomes complex protein structure. This key cellular structure will also fly for study aboard the space station, because the resolution was not all that great using the ground-grown crystals. We now have the chance to learn more about how the ribosomes actually makes proteins and clarify the whole process. This is just one of the exciting projects flying in relation to protein crystal growth.

Crystallized structure of a nucleosome core particle that was grown aboard the Mir space station. (NASA)

Crystallized structure of a nucleosome core particle that was grown aboard the Mir space station. (NASA)

This space station experimentation is a double blind study. This means that all the experiment chambers are bar coded for anonymity. We also will have exact controls done with the exact same batch of proteins prepared at the same time. The crystals will grow for the same length of time, as they are activated simultaneously in space and on the ground. When the samples come down, we will perform the entire analysis not knowing which are samples grown in space versus Earth. Only one engineer will have the key to the bar codes. When we’re completely done with the analysis, then he will let us know which were from space or ground. This will allow our study to provide definitive data on the value of space crystallization.

We also wanted to ensure that our analysis looked at a sufficient number of samples, statistically speaking, to provide conclusive data. How many data sets we collect per crystal sample will depend on the quality of that crystal. Statistically the study will be relevant in terms of how many proteins we fly, as well as how many crystals we evaluate from space and ground to make the comparison.

Astronaut Nicole Stott works with the high-density protein crystal growth (HDPCG) apparatus aboard the International Space Station. (NASA)

Astronaut Nicole Stott works with the high-density protein crystal growth (HDPCG) apparatus aboard the International Space Station. (NASA)

The microgravity environment is so beneficial because it allows the crystals to grow freely. Without the gravitational force obscuring the crystal molecules, as seen on Earth, the crystals can reveal their full form. We are giving all of these protein crystals the chance to grow to their full size in a quiescent environment. This is a very important investigation, not only because of the high number of proteins we are flying, but the statistical way we will evaluate them. Based on the results of the study, we will know if PCG in space is worth continuing.

Once the crystals come back to Earth, it will take at least one year to complete the full analysis. However, we will likely know that we’ve got some exciting results within the first three months. To publish something, it will be at least a year to complete the analysis, as we will have about 1,400 data sets to analyze. These results will determine the future of microgravity protein crystallization.

Larry DeLucas, O.D., Ph.D. (University of Alabama at Birmingham)

Larry DeLucas, O.D., Ph.D. (University of Alabama at Birmingham)

Larry DeLucas, O.D., Ph.D. is Director for the Center of Structural Biology and a professor at the University of Alabama at Birmingham. Dr. DeLucas flew as a payload specialist on the United States Microgravity Laboratory-1 flight, Mission STS-50, in June1992. His work is currently funded through NASA and the National Institutes of Health.

Space Station 15 Year Milestone — Measure and a Motivation

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In today’s A Lab Aloft, International Space Station Chief Scientist Julie Robinson, Ph.D. speaks with NASA experts in microgravity research disciplines. Together they take the opportunity of the 15 year anniversary of the station to reflect on accomplishments and discuss what’s next aboard the orbiting laboratory.

It’s hard to believe that the International Space Station has already celebrated 15 years in orbit with the anniversary of the first module, Zarya. That decade and a half included nail-biting spacewalks, and an assembly of parts designed and built around the world that was a miraculous engineering and international achievement. Our research ramped up after assembly was completed in 2011, and we are nowhere near done. In fact, with NASA Administrator Charlie Bolden’s recent announcement that the space station will continue operations till 2024, this is a time of opportunity. With full utilization already at hand, an ever-growing research community is enthusiastic about what’s next in discoveries and benefits for humanity.

A look at the International Space Station in its early days shows the Zarya module (left) connected to the second element, the US Unity module (right). (NASA)

A look at the International Space Station in its early days shows the Zarya module (left) connected to the second element, the US Unity module (right). (NASA)

I want to share with you the thoughts from some of my colleagues who have worked to enable these key achievements leading up to this milestone year for the various space station disciplines. I also asked them to share what they look forward to as we continue. With space station planned for the next decade and likely beyond, this is no time to rest, but to ramp up and make full use of this amazing laboratory.

The most important development on the space station is the emergence of a public-private partnership enabled by congress in designating the station as a National Laboratory. Managed by the Center for the Advancement of Science in Space (CASIS), this National Laboratory provides funding avenues for universal access for users, in addition to NASA-funded research. “Through the creation of CASIS, our organization is able to leverage partnerships with commercial companies, other government agencies and academic institutions to generate a variety of research capable of benefitting life on Earth,” said Gregory H. Johnson, President and Chief Executive Officer of CASIS. “The foundation of NASA-funded research discoveries on the space station helps us work with new users interested in applied research. Each year this user base is expanding due to the past success and the future promise of life sciences, materials science and Earth remote sensing.”

From a technology perspective, the design and assembly of the space station is a major international collaborative achievement in and of itself. Beyond this, the station is a unique technology test bed for everything from remote Earth sensing instruments to life support for distant destinations, such as an asteroid or Mars. As NASA’s International Space Station Technology Demonstration Manager George Nelson noted, “In these first 15 years of the space station we have managed to launch, activate, and use the state-of-the-art spaceflight systems that enable long-duration human missions. We continue to evaluate their performance and, using what we learn, we are taking steps to mature those systems in ways that better allow us to explore our solar system.”

The completed International Space Station took 115 assembly flights to complete and researchers conducted more than 1,500 investigations in the first 15 years of assembly and operations. (NASA)

The completed International Space Station took 115 assembly flights to complete and researchers conducted more than 1,500 investigations in the first 15 years of assembly and operations. (NASA)

When it comes to remote Earth sensing, the space station is not only a test bed, but an orbital platform capable of providing a constant watch on our planet, as well as our universe. William Stefanov, Ph.D., senior remote sensing specialist with NASA’s International Space Station Program Science Office, provides an overview of the station’s orbital perspective on our planet.

“During the past 15 years, the space station has become recognized as a valid and useful platform for Earth remote sensing,” said Stefanov. “Handheld camera imagery collected by astronauts from the earliest days of the station have demonstrated its usefulness as both a compliment to more traditional free-flyer sensor systems and as a vantage point in its own right, providing unique opportunities to collect both day and night imagery of the Earth system due to its inclined equatorial orbit.”

Major new instruments will be arriving during the coming years, including ISS RapidSCAT and the Cloud-Aerosol Transport System (CATS) in 2014. Looking to the future, Stefanov touched on anticipated benefits, such as those already realized by the use of the Hyperspectral Imager for the Coastal Oceans (HICO) instrument. Data from HICO is accessible to the public through the OceanColor website maintained at Goddard Space Flight Center. HICO also is now available for new data collection requests through a proposal submission process.

“The space station is now viewed by NASA and its international partners as an attractive platform to test and deploy advanced multispectral and hyperspectral passive sensor systems for land, oceanic/coastal, and atmospheric remote sensing,” said Stefanov. “We also can support humanitarian efforts related to disaster response through collection of remotely sensed information for disaster-stricken areas. The capacity to host active sensor systems, such as lidar, is also being explored. The space station is well on its way to expand its role as a test bed and become an integral part of the NASA fleet of Earth remote sensing satellites.”

Hurricane Raymond as photographed by astronaut Karen Nyberg from the vantage point of the International Space Station on October 22, 2013. (NASA)

Hurricane Raymond as photographed by astronaut Karen Nyberg from the vantage point of the International Space Station on October 22, 2013. (NASA)

While the various sensors aboard station take quite a bit of physics into account, it’s important to note that there’s plenty of physics going on inside, too. The space station also is a laboratory for fundamental physics microgravity research. I spoke with International Space Station Fundamental Physics Senior Program Executive Mark Lee, Ph.D., about station contributions in this discipline.

“In the past 15 years I think we have done a couple of really important investigations on the space shuttle before the space station came into use,” said Lee. “Specifically the Lambda Point Experiment (LPE) and the Confined Helium Experiment (CHEX) investigations. These two look at the quantum effect in a very low temperature also coupled with the dimensionality in a bulk three dimension, versus a confined limit to a two dimensional space, to see how the quantum physics behaved. These studies were provided by Mother Nature of which we cannot change, but from now on we can design our own quantum systems.”

According to Lee, quantum physics is mysterious and still barley understood, making future investigations fertile grounds for progress. “Though humanity has known of quantum physics for just a about 100 years, before the 1990s, however, we had to rely on nature to provide us with a quantum system. For instance, superconductivity, superfluid in liquid helium, even a neutron star and a black hole are gigantic star quantum systems. In the next decade on the space station we are developing the Cold Atom Laboratory (CAL) as a ‘designer’s quantum system’ apparatus.”

A multi-user facility, CAL’s design will enable the study of ultra-cold quantum gases in microgravity from aboard the space station. The primary goal is to explore extremely low temperatures, previously inaccessible, for quantum phenomena.

Artist’s concept of an atom chip for use by NASA’s Cold Atom Laboratory (CAL) aboard the International Space Station. CAL will use lasers to cool atoms to ultracold temperatures. (NASA)

Artist’s concept of an atom chip for use by NASA’s Cold Atom Laboratory (CAL) aboard the International Space Station. CAL will use lasers to cool atoms to ultracold temperatures. (NASA)

Lee continued, “The ability to study Bose Einstein condensates (BEC) and extremely cold atoms in space is a totally new dimension. With the kind of manipulation we will have in CAL, we can create different atom interactions and novel quantum configurations in such a way by manipulating individual atoms to look deeply into the quantum effect. Even Einstein’s Equivalence Principle (EEP) can be tested in space for the first time using this quantum system vs. that of previous classical ones. This is a very exciting area. This excitement, of course, is reflected in the Nobel Prize awards for related areas of study in 1997, 2001 and 2005. I can’t wait to see what happens when researchers can superbly cool and control a quantum system on the space station.”

Another exciting area of study in microgravity is that of physical science. Natural elements such as fluids and fire react quite differently and are some particularly interesting and useful areas of study in this environment. Program Executive for Physical Sciences, International Space Station Research Project Fran Chiaramonte, Ph.D., also weighed in on where we’ve been and where we are going.

When asked about the discipline of physical science in microgravity thus far, Chiaramonte responded, “I think the top achievement was the cool flames discovery. This was made when flames were detected at a temperature significantly below the known ignition temperature for the liquid droplet fuels we were studying in space. This came out of what we call the Flame Extinguishment Experiment (FLEX) where we were looking at droplet combustion in the Combustion Integrated Rack (CIR). The finding was unexpected from that research. Follow-on investigations will continue the quest to understand these flames and better define their characteristics. This has applications in the automotive industry—the findings would hand off via research publications and would be of value to them.”

Flames, like the one pictured here from the Flame Extinguishing Experiment (FLEX), burn more perfectly in microgravity, helping researchers get a better understanding of the nature of combustion in space and on Earth. (NASA)

Flames, like the one pictured here from the Flame Extinguishing Experiment (FLEX), burn more perfectly in microgravity, helping researchers get a better understanding of the nature of combustion in space and on Earth. (NASA)

Chiaramonte cited that in looking to the future, it is the early space station investigations that provide the basis for what’s next. Especially when talking about fluid physics. “In complex fluids, it started with a series of very simple experiments on phase separation between a host liquid and polymer particles. In a weightless environment, these particles will remain suspended in the solution almost indefinitely. On Earth they would settle to the bottom of the container and the experiment would be over before any meaningful science could be done. Over time the particles clumped together and separated out of the solution.”

“These precursor experiments led up to the next series of tests, called the Advanced Colloids Experiment (ACE) series,” continued Chiaramonte. “Now scientists study similar types of solutions under a microscope with a range of magnification and we are looking for a more strategic outcome. For instance, Paul Chaikin, Ph.D., is studying the self-assembly of particles, which has been a plaguing challenge for the future of advanced optical materials. In that work, they have successfully arranged one-dimensional line of particles, and have now successfully arranged a two-dimensional line of particles. This has important industrial applications.”

The gel structure, like that under investigation in the Advanced Colloids Experiment (ACE), is often dominated by fragile strands composed of many particles in a cross-section. (NASA)

The gel structure, like that under investigation in the Advanced Colloids Experiment (ACE), is often dominated by fragile strands composed of many particles in a cross-section. (NASA)

“It will take many researchers beyond Chaikin’s work,” said Chiaramonte, “but by using the space station for that kind of study, we can anticipate a major contribution in this area of three-dimensional ordering of particles and optical computing.”

From questions looking at the microscopic scale of physical phenomena, we now move on to the important minutia within our own bodies with the study of life sciences in microgravity. In speaking with Space Biosciences Division Chief Sid Sun, the research that stands out to him from the space station’s tenure involves the importance of where we’re heading next.

“In life sciences what we’ve been able to do over the last 15 years is answer at a first level the various questions that are associated with life in space,” said Sun. “Essentially how the unique environment of space, such as the microgravity and different radiation levels affect living organisms. As is typical with science, every time you answer one question, a whole other set of questions pop up, so that’s where the future of the research will take us. In particular, we’ll be studying more of the changes in the genomics of living systems.”

Astronaut Sunita Williams, Expedition 14 flight engineer, prepares a laptop for data entry during a blood draw as part of the Nutritional Status Assessment (Nutrition) study in the Destiny laboratory module of the International Space Station. (NASA)

Astronaut Sunita Williams, Expedition 14 flight engineer, prepares a laptop for data entry during a blood draw as part of the Nutritional Status Assessment (Nutrition) study in the Destiny laboratory module of the International Space Station. (NASA)

“Something that the advances in biotechnology are allowing us to do now is better understand what is happening in the basic genetic code within organisms and how that code is being expressed or not expressed in space compared to Earth,” Sun continued. “The space station allows studies of record length for a wide variety of organisms. On the space shuttle scientists were limited to from 10 to 14 days every five years. Now with the continued orbit of the space station we are able to do experiments in microgravity for months, maybe heading into half a year to a year in length, and we continuously have scientists study a wide variety of organisms. That is going to be especially critical as we look to study humans in space for multiyear missions.”

These findings flow to future areas of study, where model animals will play an important role. “Being able to study other organisms, especially rodents, will shed a lot of insights into how spaceflight will be affecting people for long periods of time. In particular, during space station assembly, pharma demonstrated that space biomedical research could enable both drug discovery on Earth and biomedical research important for astronauts. With the new Rodent Research Facility we’re developing for the space station we’re going to take that research to the next level, again taking that research into longer experiments and having more animals up there. It will be high speed compared to the experiments of the past.”

An engineering drawing of NASA’s Rodent Research Facility that will operate aboard the International Space Station. (Lockheed Martin)

An engineering drawing of NASA’s Rodent Research Facility that will operate aboard the International Space Station. (Lockheed Martin)

While model animal studies are key to human health developments, our crew also serves as test subjects for a variety of important investigations. From the beginning, our astronauts collected samples, kept journals and participated in experiments to help increase the understanding of what life in space meant for the human body.

“The first 15 years of the space station provided us with a much deeper understanding of how humans respond to six months of space flight and how to deal with those changes,” said Craig Kundrot, Deputy Chief Scientist, Human Research Program. “We have learned how to prevent or limit problems like bone loss, muscle loss, or aerobic fitness. We have discovered new changes that were not as clear in the one to two week long shuttle missions: changes in the immune system and visual impairment, for example. We have pushed technology to new limits, like the use of ultrasound for the detection of bone fractures and kidney stones.”

“In the ensuing years, we seek to overcome the remaining challenges like visual impairment,” Kundrot continued. “We also plan to progress from overcoming the challenges one at a time to overcoming the challenges with an integrated suite of countermeasures and technologies that keep the astronauts healthy and productive in future exploration missions.” These findings and the development of countermeasures and treatments are not limited to space explores, but have real world applications. From strengthening bones for those suffering from osteoporosis to boosting the immune systems of the elderly and immunosuppressed, there is much to gain from human research in microgravity.

With so much to be proud of in our 15 years of assembly and operations, it’s not surprising we have plenty to look forward to. From my perspective, I am particularly excited to see what space station researchers will discover next. Now is the time for microgravity studies to come into their own. While these future endeavors are fascinating, I am especially touched by the ways such findings return for expanded use on the ground. Whether addressing health concerns, advancing engineering designs, or inspiring the next generation, the space station may have already secured its place in history, but we are far from mission end. If anything, we have only just begun!

1037755main_Julie Robinson.jpg
Julie A. Robinson, Ph.D.
International Space Station Chief Scientist

Julie A. Robinson, Ph.D., is NASA’s International Space Station Chief Scientist, representing all space station research and scientific disciplines. Robinson provides recommendations regarding research on the space station to NASA Headquarters. Her background is interdisciplinary in the physical and biological sciences. Robinson’s professional experience includes research activities in a variety of fields, such as virology, analytical chemistry, genetics, statistics, field biology, and remote sensing. She has authored more than 50 scientific publications and earned a Bachelor of Science in Chemistry and a Bachelor of Science in Biology from Utah State University, as well as a Doctor of Philosophy in Ecology, Evolution and Conservation Biology from the University of Nevada Reno.

Model Organisms: Shining Examples for Simple, Effective Biology Research

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In today’s A Lab Aloft blog entry Camille Alleyne, Ed.D., assistant program scientist for the International Space Station Program Science Office, shares with readers the role of model organisms in microgravity research.

Have you ever thought about why biologists use the term “model organism?” This does not imply that these particular species set an example for the others in their genus. Rather, they have characteristics that allow them easily to be maintained, reproduced and studied in a laboratory. Conducting basic research on model organisms also helps researchers better understand the cellular and molecular workings of the human body, in addition to how diseases propagate. This is because the origins of all living species evolved from the same life process that is shared by all living things.

Model organisms can be plants, microbes (e.g., yeast) or animals (e.g., flies, fish, worms and rodents), all of which are widely studied and have a genetic makeup that is relatively well-documented and well-understood by scientists. Researchers favor these organisms because they grow relatively quickly and have short generation times, meaning that they swiftly produce offspring. They also are usually inexpensive to work with and are quite accessible, making them ideal for experimentation.

Aboard the International Space Station, researchers conducting studies on animal and plant biology disciplines also prefer to use model organisms. In several investigations, scientists use these test subjects to advance their knowledge of the fundamental biological processes, as they are already well-known in the specific species based on ground experimentation. 

Researchers use model organisms to study how microgravity affects cells. Examining the impacts of the space environment on an organism’s development; growth; and physiological, psychological and aging processes can lead to a better understanding of certain diseases and issues associated with human health.

 

Space radiation hitting cell DNA.(NASA)

Space radiation hitting cell DNA.(NASA)

Cells behave differently in space than on Earth because the fluids in which the cells exist move differently in the microgravity environment. The fundamental nature of the cell changes, including its shape and structure, how signals pass back and forth between cells, how they differentiate or split, how they grow or metabolize and alterations to the tissue in which cells live. Developmental biologists can learn much from these adaptations.

The Biological Research in Canisters (BRIC) experiment series of space station investigations, for instance, focuses on the area of plant biology. The study uses the thale cress (Arabidopsis thaliana) as its model organism. Scientists look at the fundamental molecular biological responses and gene expression of these plants to the microgravity environment. This small, flowering plant already has a well-sequenced genome—meaning researchers already have a map for the heredity of organism’s genetic traits. These traits are what control the characteristics of an organism, such as how it looks, behaves and develops over time.

Thale cress (Arabidopsis thaliana) seedlings. (NASA)

Thale cress (Arabidopsis thaliana) seedlings. (NASA)

Thale cress is approximately three- to seven-tenths of an inch tall and can produce offspring in large quantities in about six weeks. It also has the advantage of a small genome size—so it’s not complicated to study—and an abundance of available genetic mutants—which allows for varied areas of research focus. Specifically in the BRIC-16 investigation, Anna-Lisa Paul, Ph.D., and Robert Ferl, Ph.D., at the University of Florida in Gainesville examined the changes in the genome sequencing and DNA of these plants. Results assisted space researchers in understanding how to maintain food quality and quantity for long-duration spaceflights, in addition to how to provide and maintain life-support systems. There also are Earth applications, including understanding basic plant processes that may increase our ability to control more effectively plants for agriculture purposes.

In the area of animal biology, there are numerous investigations that use a variety of model species as subjects. In the Micro-5 investigation, principal investigator Cheryl Nickerson, Ph.D., of Arizona State University—along with co-principal investigators Charlie Mark Ott, Ph.D., of NASA’s Johnson Space Center in Houston; Catherine Conley, Ph.D., at NASA’s Ames Research Center at Moffett Field, Calif.; and Dr. John Alverdy, University of Chicago—use an organism referred to as Caenorhabditis elegans. This human surrogate model helps us better understand the risks of flight inflections to astronauts during long-duration spaceflight.

C. elegans nemotodes, or round worms, undergo examination by project scientists. The worms are descendants of those that were part of an experiment that flew on space shuttle Columbia's final mission, STS-107. (NASA/Ames/Volker Kern)

C. elegans nemotodes, or round worms, undergo examination by project scientists. The worms are descendants of those that were part of an experiment that flew on space shuttle Columbia’s final mission, STS-107. (NASA/Ames/Volker Kern)

C. elegans are free-living, transparent nematodes, or roundworms, that live in temperate soil environments. They are inexpensive and easy to grow in large quantities—producing offspring with a generation time of about three days. Members of this species have the same organ systems as other animals, making it a great model organism choice. In this study, C. elegans will be infected with the salmonella (Salmonella typhimurium) microbe, which causes food poisoning in humans and is known to become more virulent in microgravity—meaning it increases its disease causing potential. Studying this host-pathogen combination provided researchers with insight into how this bacterium will respond in space explorers, if infected. The knowledge lays a solid foundation for the development of vaccines and other novel treatments for infectious diseases.

Another model is Candida albicans, which is an opportunistic fungus or yeast that exists in a dormant state in about three of every four people. It has greater potential to become active in individuals with compromised immune systems, hence the term “opportunistic.” When active, this pathogen causes thrush or yeast infections. Easily mutated, this organism’s genes are readily disrupted for study. Principal investigator Sheila Nielsen-Preiss, Ph.D., of the Montana State University in Bozeman, used this model for the Micro-6 investigation during Expedition 34/35. As in other model organisms, the well-understood genetic makeup of this fungus made it easier for scientists to identify changes that occurred in microgravity. This led to a better understanding or the fungus’ fundamental physiological responses and their ability to cause infectious diseases.

On a larger scale, one of the human body’s major adaptations to spaceflight is the loss of bone mineral density. Understanding the mechanisms by which bones break down and build back up in this extreme environment is critical to human space exploration. In order to understand these phenomena more fully, researchers study Medaka fish (Oryzias latipaes) in the Aquatic Habitat (AQH) aboard the space station.

The above image shows an Aquatic Habitat (AQH) specimen chamber housing Medaka fish for study. (JAXA)

The above image shows an Aquatic Habitat (AQH) specimen chamber housing Medaka fish for study. (JAXA)

These model animals found in Asia are used extensively in biological research. They are vertebrates—meaning they have backbones—making them a good choice for studying bone activity. Medaka also have a well-mapped genome, a short gestation period and reproduce extremely easily. They are resilient and can survive in water of various levels of salinity.

In the Medaka Osteoclast investigation, principal investigator Akira Kudo, Ph.D., of the Tokyo Institute of Technology, along with co-principal investigators Yoshiro Takano, DDS, Ph.D., of the Tokyo Medical and Dental University; Keiji Inohaya, Ph.D., of the Tokyo Institute of Technology; and Prof. Masahiro Chatani of the Tokyo Institute of Technology, studied the process by which bone breaks down via the activity of bone cells known as osteoclasts. The transparency of the fish gave researchers a view into the mechanism of this process that would not be possible with other fish species. The goal of this research is to advance our knowledge on human bone health, leading to development of treatments and countermeasures for both astronauts living in space and patients suffering from osteoporosis on Earth.

In the coming year, the space station will add two new facilities as research resources to house a couple of distinct model organisms. The first is a fruit fly (Drosophila melanogaster) habitat. This type of insect is one of the 1,200 species in the genus of flies that is particularly favorable in genetic research. You may be surprised to know that the genes of D melanogaster are very similar to those of humans. More than half of our genes that map to diseases have been found to match those of fruit flies.

Since fruit flies reproduce quickly and their genome is completely sequenced, they serve as good models to study diseases in a much shorter time than it would take via human research. In the context of human spaceflight, scientists will continue to use fruit flies as a model to test gene expression in the space environment, adding to work done on the space shuttle.

Sharmila Bhattacharya, Ph.D., is the principal investigator for the Fungal Pathogenesis, Tumorigenesis and Effects of Host Immunity in Space (FIT) fruit fly investigation. In this image, Bhattacharya is inspecting the fly experiment containers before flight. (NASA)

Sharmila Bhattacharya, Ph.D., is the principal investigator for the Fungal Pathogenesis, Tumorigenesis and Effects of Host Immunity in Space (FIT) fruit fly investigation. In this image, Bhattacharya is inspecting the fly experiment containers before flight. (NASA)

The second habitat coming to the space station will house rodents. Mice (Mus musculus) are the most widely known of the model species in scientific research, because their genetic code and physiological traits are very similar to humans. They are vertebrate mammals with a 10-week generation time. Their genome is very well-sequenced and understood, and they are easy to mutate and analyze. 

Mice, more than any of the other animal model organism mentioned here, allow researchers to study beyond just the cellular cycle. They have the opportunity to advance their fundamental understanding of other human systems such as the immune, cardiovascular and nervous systems, to name a few. Mice afflicted with various diseases, including osteoporosis, cancer, diabetes and glaucoma, can lead researchers to findings that advance treatment options.

These developments and findings from past, present and future investigations aboard the space station continue to enable biologists in their studies. As researchers better understand the adaptation of model organisms in a microgravity environment, they can facilitate future ways doctors will manage human health, both in space and on Earth.

Camille Alleyne, Ed.D., is an assistant program scientist for the International Space Station Program Science Office at NASA’s Johnson Space Center in Houston.

Camille Alleyne, Ed.D., is an assistant program scientist for the International Space Station Program Science Office at NASA’s Johnson Space Center in Houston. She is responsible for leading the areas of communications and education. Prior to this, she served as the deputy manager for the Orion Crew and Service Module Test and Verification program.  She holds a Bachelor of Science degree in Mechanical Engineering from Howard University, a Master of Science degree in Mechanical Engineering (Composite Materials) from Florida A&M University, a Master of Science degree in Aerospace Engineering (Hypersonics) from University of Maryland, and a doctorate in Educational Leadership from the University of Houston.

Could You Choose Just One? Looking Beyond the Top Ten Space Station Research Results Countdown

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In today’s A Lab Aloft entry International Space Station Program Scientist Julie Robinson, Ph.D., concludes her countdown of the top research results from the space station.

I’ve shared with you my top ten research results from the International Space Station in this blog series, and this is only the middle of the mission. With the space station scheduled to continue operating until at least 2020—and likely beyond—we continue with investigations that present us with more interesting facts and findings. Even as you read this entry, hundreds of investigations are active in orbit.

Whatever missions we look to tomorrow—including travel to an asteroid and Mars—they absolutely depend on the success of the space station. That is because the station was developed to return benefits and discoveries to us here on Earth. How we use the space station, both in our success as an industry and in returning benefits back to our nations and our economies, impacts everybody. If we don’t all take ownership to share this story, it makes our stakeholders look at our future ideas and say, “well yeah, that’s great for you, but what’s in it for the rest of the country.”

The International Space Station seen against the backdrop of the Earth, as photographed by the STS-130 crew aboard space shuttle Endeavour. (NASA)

The International Space Station seen against the backdrop of the Earth, as photographed by the STS-130 crew aboard space shuttle Endeavour. (NASA)

I was originally challenged to pick a set of top 10 research results by the organizers of an aerospace industry meeting, the International Astronautical Congress. Now I would like to challenge not only the members of the aerospace community, but all of those reading this blog who may one day benefit from this orbiting laboratory—that means you. Please take home one of these top ten research facts to share with your family, friends and colleagues. There are many more benefits and results than just those I highlighted, but it’s a good place to start.

Of the examples I gave you in this series, be ready to own the one that you choose. If you are talking with a government official, the press, your students, your family, that stranger sitting next you to on a plane, whomever you encounter, be prepared to share. The space station is our pinnacle of human spaceflight, it is our example of international cooperation and it is doing outstanding things in science yesterday, today and tomorrow. You don’t have to be a scientist to share the wonder and the value of the science we are doing there with others.

To make the difficult choice of a top 10 possible, there are a lot of things I didn’t include in the list. Sometimes, these were more technology spinoffs than research results. I also didn’t include the specific knowledge being gained for the purposes of future exploration—that could be another top 10 by itself. The use of space station ultrasound techniques in saving lives of women and their unborn children around the world, for instance. New remote ultrasound practices are being tested in developing nations, but this was a pure spinoff—no additional research needed—which is why it did not make my list. I also did not touch on the space station technology used today for air purification in daycares or the fresh water technology from station. Again, I did not select these primarily because they are pure spinoffs.

WINFOCUS and Henry Ford Innovation Institute members, Dr. Luca Neri and Alberta Spreafico work with Kathleen Garcia from Wyle Engineering to help train Dr. Chamorro from the rural community of Las Salinas, Nicaragua, using the ADUM and tele-ultrasound applications. (WINFOCUS/Missions of Grace)

WINFOCUS and Henry Ford Innovation Institute members, Dr. Luca Neri and Alberta Spreafico work with Kathleen Garcia from Wyle Engineering to help train Dr. Chamorro from the rural community of Las Salinas, Nicaragua, using the ADUM and tele-ultrasound applications. (WINFOCUS/Missions of Grace)

These examples are equally impactful and perhaps even more quickly connected to saving lives here on Earth. I encourage you to learn more by visiting our resources as we continue to share new developments, findings and benefits from space station research. Why limit this topic to so few as just ten; quite frankly, why limit the conversation to just the aerospace industry?

Amazingly enough, people you know have not heard about the space station, so we all need to take responsibility for sharing this message. There are some great resources we’ve put together as a partnership for you, so you won’t have to just remember the words you read here. You can look at the space station benefits for humanity website, which has been translated into multiple languages. You also can keep up on all the great things going on by following space station research on nasa.gov, revisiting this A Lab Aloft blog and by following our Twitter account: @ISS_Research.

I’d like to close by pointing out how sharing a view of the space station over your town can have a big impact on the people in your own orbit. My husband does not work in aerospace; he’s in the insurance industry. I remember one time there was going to be a great overpass of the space station in Houston, and I suggested to him that he go up on top of his building to see it. He sent an email around his office as an invitation and he ended up on the roof of the building with his colleagues and a senior executive. Together they watched this amazing space station pass. While looking up, the executive leaned over to my husband and said, “that was really neat! I had no idea we had people in space.”

One of our “people in space,” NASA astronaut Karen Nyberg works with the InSPACE-3 colloid investigation in the Microgravity Science Glovebox. (NASA)

One of our “people in space,” NASA astronaut Karen Nyberg works with the InSPACE-3 colloid investigation in the Microgravity Science Glovebox. (NASA)

The fact is that leaders in the world of business outside of aerospace are not paying attention to what we are doing. Science policy position and analysis can have scant information about what is really going on and what we are accomplishing. In the din of public policy debates, it is sometimes hard for us to get people hear about the good news. Two things that we really need to share with everyone are that the space station is up there with humans working on orbit, and that it is bringing back concrete benefits for use here on Earth. These returns make our economies stronger, make our individual lives better and save peoples’ lives. That really is the core of space exploration and why we do it.

Here, again, are my top ten space station research results in review.

10. Preventing the loss of bone mass in space through diet and exercise

9. Understanding mechanisms of osteoporosis and new ways to treat it

8. Hyperspectral imaging for water quality in coastal bays

7. Colloid self assembly using magnetic fields for development of nanomaterials

6. A new process of cool flame combustion

5. Pathway for bacterial pathogens to become virulent

4. Forty-three million students and counting

3. Dark matter is still out there

2. Robotic assist for brain surgery

1. New targeted method of chemotherapy drug delivery with breast cancer trials now in development

Thank you for sharing!

Julie A. Robinson, Ph.D.
International Space Station Program Scientist

Top Space Station Research Results Countdown: One, New Targeted Method of Chemotherapy Drug Delivery; Clinical Breast Cancer Trials Now in Development

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In today’s A Lab Aloft entry, International Space Station Program Scientist Julie Robinson, Ph.D., continues her countdown to the top ten research results from the space station, recently presented at the International Astronautical Conference in Beijing, China. Be sure to check back for daily postings of the entire listing.

Last, but not least in my International Space Station top ten countdown is a new targeted method of chemotherapy drug delivery, with breast cancer trials now in development. This treatment has the potential to change the landscape for how we address cancer—a devastating illness that has touched many of our lives—which is why the result ranks number one on my list.

This research goes clear back to Expedition 5 in 2002 when astronaut Peggy Whitson was aboard the space station for the first time. Scientists were interested in looking at whether or not microencapsulation—basically, building a microballoon that could contain a small amount of a chemotherapy drug—could do a better job of delivering that treatment to a tumor. There were some theoretical models that suggested that if you didn’t have gravity in the way, you could assemble these microballoons with better properties to streamline delivery right to the tumor site.

Single cell microencapsulation. (NASA)

Single cell microencapsulation. (NASA)

The Microencapsulation Electrostatic Processing System (MEPS) investigation proved that if you took gravity out of the equation, you could actually make these microencapsules with the right kind of properties. But of course you can’t make clinically useful quantities in space. So scientists spent the next five years perfecting a way to make these microballoons in clinically relevant quantities and clinical purity on the ground. Those technologies were licensed to a commercial company, which then began developing microencapsulation as a therapeutic measure. That process in itself can take decades.

If you asked me six months ago, I would not have even included this particular topic in the top ten. The reason it’s back on the list is because of the new work being done to adapt this technology for treating breast cancer. Clinical trials also appear to be getting closer, with MD Anderson Cancer Center in Houston. Researchers are finishing out the work that it takes to get FDA drug approval, so this is looking more promising for making it through to development, and finally to patient care.

Dr. Morrison with Microencapsulation Electrostatic Processing System (MEPS) flight hardware ready to pack for the International Space Station UF-2 mission. (NASA)

Dr. Morrison with Microencapsulation Electrostatic Processing System (MEPS) flight hardware ready to pack for the International Space Station UF-2 mission. (NASA)

As you can see from the span of the top ten, in research things go up and down and these developments can take decades. So the topic of targeted drug delivery for cancer treatment may fall off the list again, or it may successfully go all the way to the finish line. I think for sheer persistence in taking a great space station result and making it into something with lifesaving potential, the researchers and doctors working on this topic deserve credit for their endeavors. This is why they are number one on this year’s countdown.

Julie A. Robinson, Ph.D.
International Space Station Program Scientist

Top Space Station Research Results Countdown: Two, Robotic Assist for Brain Surgery

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In today’s A Lab Aloft entry, International Space Station Program Scientist Julie Robinson, Ph.D., continues her countdown to the top ten research results from the space station, recently presented at the International Astronautical Conference in Beijing, China. Be sure to check back for daily postings of the entire listing.

Number two on my countdown of International Space Station research results shows just how versatile the developments we’ve made for space can be when reexamined and repurposed for use on the ground. In this case, robotic assist for brain surgery is giving surgeons a helping hand to save the lives of patients with otherwise inoperable brain tumors and other diseases. I include this example not only as a technology spinoff, but to highlight the fact that it took a lot of research back on the ground to make this a reality.

The International Space Station Canadarm (pictured here) led to a technology spinoff to assist with brain surgery on Earth. (NASA)

The International Space Station Canadarm (pictured here) led to a technology spinoff to assist with brain surgery on Earth. (NASA)

The aptly named neuroArm technology came from the space station’s robotic arm. The Canadarm was developed by MDA for the Canadian Space Agency. For use in space, the arm needed to be resilient, perform well in doing critical space station assembly tasks without failing, and be able to continue operations while taking radiation hits. These specific traits made this technology ideal to translate for developing a robotic arm surgical assist. Doctors likewise needed equipment that they could trust to function consistently and that could go right inside an MRI and still operate effectively.

Paige Nickason, the first patient to have brain surgery performed by a robot, points to the area on her forehead where neuroArm performed surgery to remove a tumor from her brain. (Jason Stang)

Paige Nickason, the first patient to have brain surgery performed by a robot, points to the area on her forehead where neuroArm performed surgery to remove a tumor from her brain. (Jason Stang)

The neuroArm allows robotic guidance of brain surgery with keep out zones, such that physicians can remove tumors too close to sensitive areas of the brain for surgery by hand alone. The combination of having the MRI, the robotic guidance and the keep out zones allows the surgeon to do the procedure safely, without impacting the other areas of the brain. It is no wonder that Garnette Sutherland, M.D., University of Calgary, was recognized for outstanding results on advancing neurosurgery through space technology – named a top medical application from the space station for 2012.

The use of neuroArm has led to some extraordinary patient outcomes. The first set of research publications on the clinical trials published recently in the Journal of Neurosurgery for the initial 35 patients; many other patients have now had tumors successfully removed. This is a really exciting technology spinoff that also led to research results back here on Earth that are saving lives.

Julie A. Robinson, Ph.D.
International Space Station Program Scientist

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