Intro to CASIS Comparing the NASA Mission / CASIS Mission Our current portfolio (pie chart slide; commercial company slide) What drew me to this mission? Embrace our chance to make a difference in utilizing the space station and LEO development We are the best advocates for the station, space and lab. This won’t get done without your help
Repeat customers include Eli Lilly, Merck, Proctor & Gamble Portfolio ranges from life sciences, material and physical sciences, tech development and Earth observation/remote sensing CASIS as an organization does not have an abundance of financial resources so it is incombent upon us to work with leaders in the research community who do have financial resources to fund potential opportunity on the ISS NL.
to accelerate or enhance product design
The microgravity environment onboard the space station has significant effects across many scientific disciplines, from physical and materials science to life sciences It affects complex and basic processes in the physical sciences, and It influences biomedical sciences from the level of body systems down to cell processes
These effects can advance our knowledge of Earth-based processes, including those relevant to commercial applications. Many research questions studied in space are difficult or impossible to investigate on Earth, particularly if experiments require observations over more than a brief length of time.
Bioscience: Microgravity induces a vast array of changes in organisms ranging from bacteria to humans, including changes in gene expression profiles and 3-D aggregation of cell cultures into tissue-like structures Example in image: improved aggregation of cancer cells
Physical Sciences: Effects are driven mainly by the absence of buoyancy-driven convection, which is dependent on gravity. Fluid dynamics, combustion, and phase changes are all heavily influenced by this change. Examples in images: changes in fluid movement and flame structures
Example SUCCESS STORIES: Experiments in space studying gene expression in salmonella revealed a gene involved in infectiousness, leading to the development of a candidate vaccine. Drug-delivery “microcapsules” optimized in microgravity were reproduced on Earth and are currently in use in clinical trials at MD Anderson Cancer Center and the Mayo Clinic. When crystallized on station, a protein involved in Duchenne muscular dystrophy produced a more detailed 3-D structure that led to the development of a candidate treatment, which has completed animal testing and is now in human clinical trials.
Images: Colon carcinoma cells grown in a NASA Bioreactor flown on the STS-70 Space Shuttle in 1995 flight versus ground control experiments. Cells grown in microgravity aggregate to form masses that are larger and more similar to tissue found in the body. Comparison of thermocapillary flows on Earth (top) and in micogravity (bottom). The flow pattern (indicated by the white areas) in the Earth-based experiments is only evident on the fluid's surface, while the flow pattern in microgravity encompasses the entire fluid.
Nicole Stott works with a Protein Crystal Growth experiment (The results described below are the result of a joint JAXA-Roscosmos investigation (JAXA/Roscosmos science, JAXA hardware).
Small images; Left: Earth-grown H-PGDS crystal Right: ISS-grown H-PGDS crystal Inset: H-PGDS/HQL-79 complex grown in space, revealing previously unknown water molecule.
General Public: There are more than 100,000 proteins in the human body. The unique shape of those proteins gives us clues about their function. In fact, pharmaceuticals are designed based on this knowledge. The more that is known about the shape of a protein, the easier it is to design a drug to specifically and efficiently interact with that protein. We can grow protein crystals on Earth to study them, but gravity distorts the fragile structures. Crystals grown in microgravity are larger and have fewer defects. In one example, scientists grew a protein associated with Duchenne Muscular Dystrophy along with an inhibitor protein onboard the space station. A larger, more accurate structure was revealed. Using this new structural information, researchers have developed an even more potent form of the inhibitor for Duchenne, which is now a leading candidate for the treatment of this debilitating disease.
Scientific Community: Muscular dystrophy is an inherited muscle disorder that causes muscular atrophy and speeds the progression of muscular deterioration. Human hematopoietic prostaglandin D synthase (H-PGDS) has been shown to play a major role in advancing the progression of Duchenne muscular dystrophy. During previous ground-based protein crystal growth studies of H-PGDS protein, researchers found that HQL-79 (an oral anti-inflammatory drug) binds to the catalytic pocket of the H-PGDS protein, thus inhibiting H-PGDS function, making HQL-79 a leading candidate for the treatment of Duchenne. On ISS, the microgravity environment allowed researchers to grow a larger H-PGDS/HQL-79 inhibitor complex, resulting a structure that revealed a hidden water molecule that had never before been found. Using this new structural information, researchers have developed an even more potent form of HQL-79 inhibitor for Duchenne which is currently being tested in animals before humans.
More info on this experiment: http://www.nasa.gov/mission_pages/station/research/experiments/339.html
Karen Nyberg controls the InSPACE-3 investigation in the Microgravity Sciences Glovebox (MSG) (PI: Eric Furst, University of Delaware, DE).
General Public: Colloids are tiny particles suspended in a solution, which are critical in household products such as medications, detergents, paint, as well as in industrial processes. A unique type of colloid is studied in the Investigating the Structure of Paramagnetic Aggregates from Colloidal Emulsions (InSPACE) collection of experiments. Specifically, magnetorheological fluids — fluids that change their viscosity in magnetic field. These fluids are classified as smart materials which transition from a liquid to a solid-like state by the formation and cross-linking of microstructures in the presence of a magnetic field. On Earth, these materials are used for vibration damping systems that can be turned on or off. These damping systems are already in use in some bridges and buildings in earthquake-prone regions (ISS research may improve these systems).
Scientific Community: Observations of the microscopic structures yields a better understanding of the interplay of magnetic, surface, repulsion forces, and particle shape between particles in magnetically responsive fluids. Microgravity study aboard the space station slows down the movement of these colloidal mixtures, allowing researchers to understand how they interact, and then use this knowledge to control the tiny particles on the ground. You can’t do these experiments on Earth because the nanoparticles would settle out too quickly due to gravity.
Middle Image: Structure evolution in an MR fluid over time while an alternating magnetic field is applied. The top image shows the fluid after 1 second of exposure to a high-frequency-pulsed magnetic field. The suspended particles form a strong network. The next images down show the fluid after 3 minutes, 15 minutes, and 1 hour of exposure. The particles have formed aggregates that offer little structural support and are in the lowest energy state. Full Story: http://www.nasa.gov/mission_pages/station/research/news/InSPACE_particles.html
Chris Cassidy operates the Combustion Integrated Rack (CIR) for the Flame Extinguishment Experiment (PI: Forman Williams, University of California San Diego, CA).
General Public: The familiar teardrop shape of a flame is an effect caused by gravity. Hot air rises, and draws fresh cool air behind it. This is called buoyancy-driven convection. In microgravity, flames burn differently – they form spheres which burn slower and simpler, which allow us to better understand small details to refine theoretical models and numerical simulations. Understanding combustion helps us to fight fires, use fuel more efficiently, and produce less pollution.
Scientific Community: In the FLEX investigation, combustion and extinction of liquid fuel droplets are characterized with the intent of testing the effectiveness of various fire suppressants in microgravity, to provide direction for design of future spacecraft fire suppression testing and systems. A recent surprising discovery was made with heptane. Ordinary, visible heptane flame ball burned at a high temperature ~1400 deg F. As the heptane flame ball cooled and began to go out, “cool flame” combustion took over and continued to burn at ~600 deg F; with completely different chemistry. Normal flames produce soot, CO2 and water. Cool flames produce CO and formaldehyde. Why do this research? These results could lead to cleaner auto emissions. Instead of a spark inside an internal combustion engine cylinder, engineers could design a gentler, less polluting combustion process throughout the chamber.
Full story: http://www.nasa.gov/mission_pages/station/research/news/cool_flame.html
International Space Station Expedition 42 Commander Barry "Butch" Wilmore shows off a ratchet wrench made with a 3-D printer on the station. The wrench and other parts will return to Earth for testing at NASA’s Marshall Space Flight Center in Huntsville, Alabama. The ratchet wrench was designed by Noah Paul-Gin, an engineer at Made In Space Inc., a northern California company that NASA contracted to design, build and operate the printer. Paul-Gin created a 3-D model of the ratchet and made several wrenches, such as the one shown here on an identical printer.
Kim, H., Phung, Y., & Ho, M. (2012). Changes in Global Gene Expression Associated with 3D Structure of Tumors: An Ex Vivo Matrix-Free Mesothelioma Spheroid Model. PLoS ONE, 7(6), e39556. doi:10.1371/journal.pone.0039556
Xia Y, Nivet E, Sancho-Martinez I, Gallegos T, Suzuki K, Okamura D, Wu MZ, Dubova I, Esteban CR, Montserrat N, Campistol JM, Izpisua Belmonte JC. (2013). Directed differentiation of human pluripotent cells to ureteric bud kidney progenitor-like cells. Nat Cell Biol. 15(12):1507-15.
Workshop Objectives for the Iss National Lab
THE ISS NATIONAL LAB
Michael Roberts, PhD
CASIS, Deputy Chief Scientist
25 October 2016
by access to space:
scientific research in
the life and physical
sciences that takes
advantage of unique
aspects of the space
in the life and
needed to develop
by operation in a
Science in space for
the benefit of Earth.
To advance exploration of
the solar system, scientific
research, and enable
commerce in space.
The use of ISS in support of
respective national goals.
THE ISS U.S. NATIONAL LAB
The ISS U.S. National Lab provides opportunity for research and discovery
targeted to a definitive impact on Earth
The opportunities are wide-ranging:
EVOLVING ISS NATIONAL LAB – BIG PICTURE
• Commercial engagement – 71% of FY15 CASIS-sponsored
research projects represent commercial companies
• Robust portfolio – CASIS has evaluated more than 200 proposals
• Awarded more than $20M in seed money to ~100 projects
• Sponsored program model – Leveraged the financial resources of
other outlets with our ability to manifest ISS National Lab flight
• NSF – $1.8 million investment in fluid physics R&D
• NIH - $12 million microphysiological systems (chips in space) R&D
• Network building – Developing/managing partnerships across
targeted geographic ecosystems
• e.g., MassChallenge in Boston, Houston Angel Network in Houston,
Space Angels Network in SoCal, Lux Capital in CA
WHO WE ENGAGE
MUSCLE / BONE
AND ON THE HORIZON…
Life Sciences Physical Sciences
SPONSORED PROGRAMS: FLIGHT AND STEM
• Tailored program aimed at solving an
organization’s challenge and/or driving new
innovation by finding and flying cutting edge
• $0 program cost
• $7.4 million dollar value
• Minimal Time to investment
• Program elements
• Identification of and outreach to best research and tech dev
• Advertising and outreach to pool of relevant innovators
• Information and education sessions on program goals
• Cross-disciplinary and collaborative solution development
• Subject matter expertise
• Translation of ground based goals to space
• ‘Space is in It’ Markings
• Custom Flight Patch
• Launch participation
• Media outreach
• STEM program wrappers
FLUID DYNAMICS SPONSORED PROGRAM –
USING A SOLICITATION AS A VEHICLE
• CASIS-NSF released joint program on December 10, 2015
• 48 preliminary review forms were submitted to CASIS
• CASIS invited 27 to submit a full proposal to NSF in March (all 27 submitted)
• NSF Science Review Panel will occur on May 16-17
• Final funding determination will be handled by both parties
• Anticipate announcing 4-6 awards by 2016 ISS R&D Conference in July ($1.8M in grants)
• Potential for further collaboration with NSF in other scientific areas
GALACTIC GRANT SPONSORED PROGRAM –
USING A COMPETITION AS THE VEHICLE
Galactic Grant Competition
Alters many observable phenomena
• Extreme Conditions of Space
Extreme heat and cold cycling
High energy radiation
• Vantage Point/Earth Observation
Orbital path over 90% of Earth’s population
Altitude ~240 mi (400 km)
Improved spatial resolution
Variable lighting conditions
Flame StructureThermo-capillary flows
NEW FRONTIERS FOR CUTTING-EDGE SCIENCE
CASIS User Support Includes:
• Brainstorming with researchers to identify optimal projects
• Translation of ground based science goals to space based environment
• Use of labs (if needed) at Kennedy Space Center and other NASA facilities
• Logistics for data acquisition, sample recovery, data/software interfaces
• Transportation to and from the ISS
• Support of real-time, in-orbit operations (video, astronaut involvement, etc)
• Working with 3rd Party hardware companies to provide hardware and facilities
that support the project
• Coordinating contingency plans to preserve science objectives
Images courtesy of NASA
FOCUSED RESOURCES ENABLING DISCOVERY
SUBSIDIZED VALUE OF $7.4 MILLION
RETHINK YOUR SCIENCE IN SPACE…
Convection Buoyancy Sedimentation
• Balance disorders
• Cardiovascular deconditioning
• Decreased immune function
• Muscle atrophy
• Bone loss
Image Courtesy: Dr. Clarence Sams
Humans Plants Cells Microbes
RETHINK LIVING SYSTEMS…
CONVECTION SEDIMENTATION BUOYANCY
Protein Crystal Growth - Improved structure of biological proteins grown in microgravity
can lead to better pharmaceuticals on Earth.
LACK OF CONVECTION – BUOYANCY - SEDIMENTATION
Property Measurements & Behavior- Critical properties can be measured more
accurately in microgravity, leading to more exact design models
Nanotechnology - Smart fluids
change stiffness in response to
magnetic fields and are already
used in buildings and bridges
in earthquake-prone regions.
Earth Microgravity Flame Ball on ISS Cool Flame on ISS
Combustion - Studies on flame behavior and fuel mixtures on the space station may lead
to improved fuel efficiency and reduced pollution on Earth.
Materials Exposure - Coatings
tested outside the space
station for degradation.
Extreme heat and cold
(+250 to -250 C), ultra-vacuum,
atomic oxygen and radiation
Manufacturing- The first 3-D printer ever tested in orbit may help to manufacture parts
quickly and cheaply in space.
ISS NL LIFE SCIENCE FOCUS AREAS: PROJECTS
SPAN THE DRUG DEVELOPMENT CYCLE
Stem Cell research
(in vivo, cell
Clinical CommercializationPre-ClinicalLead Discovery
CASIS INDUSTRIAL SECTOR
FOCUS AREAS & MATERIALS RESEARCH VERTICALS
Petroleum Consumer Products Advanced MaterialsIndustrial Chemicals
DISEASE MODELS FOR THE ISS NATIONAL LAB
25 Images: Courtesy of the National Institutes of Health unless otherwise noted.
Image: Ranga et al. (2014) Advanced Drug Delivery Reviews. 70:19–28
S. mediterraneaG. tigrina
Non-human Model Organisms
3D Mammalian Cell-based, Spheroid,
and Organotypic Models
N. crassa S. cerevisiae
ARCHAEA BACTERIA VIRUSES Xenopus laevis iPS cellsFibroblast
Image: Kim et al. (2012) PLoS ONE.
TUMOR SPHEROID MODELS ORGANOTYPIC MODELS
Human stem cells grown into
early-stage ureteric buds,
kidney precursors. Mouse
embryonic kidney cells (red)
coaxed human stem cells to
form buds (blue and green).
(Xia et al. (2013) Nature Cell
EFFECTS ON BODY SYSTEMS
Bone mineral density decreases more
rapidly in space than on Earth
• Accelerated model of disease/aging
Muscle mass and strength decline in
• Phenotypes similar to disuse and age-
related muscle atrophy
Images courtesy of NASA
Osteoprotegerin testing in mice on Shuttle
Myostatin knockout Normal
Experiments involving muscular dystrophy therapeuticsNumerous changes to the immune system occur,
mainly related to immunosuppression, and
research has shown increased virulence of
PREVIOUS CASIS RFP: STEM CELLS
• Improved 3-D tissue growth and global changes in gene expression
• Ability to either maintain pluripotency or improve differentiation
Images courtesy of NASA
Cell constructs grown in a rotating bioreactor on Earth become too large to stay suspended.
In orbit, the cells remain suspended
• Delivery systems/microencapsulation
• Testing (e.g., in vivo, cell culture, screening
• Protein crystal growth (PCG)
Previous RFP: Advancing
Microgravity (2012) sought projects aimed
at improving crystallization of medically
Nucleosome core particle
Microcapsules synthesized in space
Images courtesy of NASA28
MACROMOLECULAR CRYSTAL GROWTH
Larger, more highly ordered crystals of proteins and large
Acta Cryst. (2010). F66, 846–850
H-PGDS crystallized with novel inhibitors
Source: Yoshido Urade, Osaka Bioscience Institute
HQL-79 , part of a candidate treatment for inhibiting the effects of
Duchenne’s muscular dystrophy
FLUID DYNAMICS & TRANSPORT PHENOMENA
• Multiphase Flows
• Capillary Flow
• Surface Tension
• Separation and Agglomeration
• Interfacial Behavior
3D rendition of the diffusion of nanoparticles through a
Image courtesy of MHRI
Water droplet on a leaf on
the BIO-5 Rasteniya-
experiment. Photo taken
on March 9th, 2003.
To identify basic science requirements, strategic research objectives,
and optimum disease models for a sustainable microbiome,
immunome, and disease research program aboard the International
Space Station U.S. National Lab. Based on the current status of
microbiome research, we intend to define focus areas for research,
resources (flight/ground) and hardware required to support research
in microgravity with consideration for STEM education and
collaborative funding opportunities.
Ultimately, this workshop will lead to an ISS National Laboratory
initiative for microbiome research in microgravity that provides a
platform for accelerating discovery and translational research for
industry, other government agencies, and academic institutions.
THE AFTERNOON AGENDA
12:30 – 2:30 Concurrent Break-Out Sessions
Session 1 – The National Microbiome Initiative and interagency research on ISSNL.
Session Lead: Elizabeth Stulberg
Session 2 – Microbiology of the built environment: Earth and Space.
Session Lead: Julie Robinson
Session 3 – Microbiology of the human environment.
Session Lead: Mark Ott
Session 4 – What's Next for Microbiome Research in Space?
Session Lead: Michael Roberts
2:30 – 2:45PM BREAK
2:45 – 3:45PM Session Leads Present Summary
3:45 – 4:30PM Next steps and Closing
Explore CASIS Online:
Photos provided courtesy of NASA. CASIS is the sole manager of the U.S. National Laboratory on the International Space Station.
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