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LEO Commercialization: Space-Based Research
and Development and Manufacturing
• ADAM BLUESTEIN, CONTRIBUTING INNOVATION WR...
Large-volume protein crystal growth
for neutron macromolecular
crystallography
Joseph D. Ng
University of Alabama
in Hunts...
Disease
Target
Identification/
Bioinformtics
Protein Sequence
Structure-based Drug Design Process
Protein
Production
Cryst...
Structure-based Drug Design Process
StructureLead Structure
Chemoinformatics
Biochemical Assays
Cell-based Assays
Animal T...
107,324
As of Thursday 30 June, 2016
<100 Structures determined by
neutron diffraction (<0.08% of total)
50% Of the atoms in a protein are hydrogen and the majority of the proteins do not have
structural placement and biologica...
Munshi et al. (2012). Rapid visualization of hydrogen positions in protein
neutron crystallographic structure. Acta Cryst....
Inorganic Pyrophosphatase (IPPase)
+
IPPase
Mg2+
ATP
+
AMP
Granada crystallization box(GCB) and facility (GCF). Counter
diffusion crystallization can be performed in capillary fille...
A B C D
E
F G
1 2
3
1 2 3
Ground Microgravity
A
B
IPPase + Mg+2 (Acetate)
Length of capillary = 70mm; Inner diameter = 2mm
Original sample code: 6C
Ground Microgravity
A
B
IPPase + Mg+2 (Acetate)
Length of capillary = 70mm; Inner diameter = 2mm
Original sample code: 5C
0.00
5.00
10.00
15.00
20.00
25.00
30.00
35.00
40.00
45.00
1.502.503.504.505.506.507.508.50
I/σ
Resolution (Å)
B
Space
Earth
I/σ
Resolution (Å)
C
0.00
10.00
20.00
30.00
40.00
50.00
60.00
70.00
80.00
1.502.002.503.003.504.004.505.005.50
Space
Earth
H2O
H2O
H2O
H2O
H2O
D2O
D2O
D2O
D2O
D2O
Ca2+
Ca2+
Tyr56 Tyr56
Lys105
Lys105
H2O
H2O
H2O
H2O
H2O
D2O
D2O
D2O
D2O
D2O
Ca2+
C...
NIH and CASIS Partnership on Microphysiological Systems
for Translational Research in Space
Danilo A. Tagle, Ph.D.
Associa...
Human Tissues-on-Chips
NIH-CASIS Coordinated Program in Tissue-on-Chips
Systems for Translational Research in Space
• Goal: NCATS has established...
NIH-CASIS Coordinated Program in Tissue-on-Chips
Systems for Translational Research in Space
• Potential impact: Understan...
W HERE W E’VE BEEN
THE NEAR TERM FUTURE OF THE SPACE INDUSTRY IS LEO COMMERCIALIZATION
NASA and other government agencies
have been incredibl...
FIBER
LEO Commercialization: Space-based Research and Development and Manufacturing
LEO Commercialization: Space-based Research and Development and Manufacturing
LEO Commercialization: Space-based Research and Development and Manufacturing
LEO Commercialization: Space-based Research and Development and Manufacturing
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LEO Commercialization: Space-based Research and Development and Manufacturing

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By the end of 2017, NASA plans to purchase both crew and cargo delivery services to the International Space Station from commercial suppliers. Near the planned end-of-life for ISS, NASA intends to transition low Earth orbit (LEO) operations from government-led to commercially-driven as a result of greater involvement from the private sector. CASIS has seen increasing demand for use of the ISS National Lab to support research and development in numerous fields. This session will highlight the R&D opportunities in low Earth orbit ranging from LEO commercialization efforts related to advancing protein crystal growth studies for drug discovery and delivery; stem cell, organs-on-chips, and vascularized tissue research for organ bioengineering; and use of 3D printing capabilities and superior optical fiber manufacturing for on-orbit production.

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LEO Commercialization: Space-based Research and Development and Manufacturing

  1. 1. LEO Commercialization: Space-Based Research and Development and Manufacturing • ADAM BLUESTEIN, CONTRIBUTING INNOVATION WRITER, FAST COMPANY (MODERATOR) • DR. JOSEPH NG, PRESIDENT, IXPRESSGENES; ASSOCIATE PROFESSOR, UNIVERSITY OF ALABAMA-HUNTSVILLE • DR. DANILO TAGLE, ASSOCIATE DIRECTOR, SPECIAL INITIATIVES, NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES, NATIONAL INSTITUTES OF HEALTH • ANDREW RUSH, PRESIDENT, MADE IN SPACE SPEAKERS:
  2. 2. Large-volume protein crystal growth for neutron macromolecular crystallography Joseph D. Ng University of Alabama in Huntsville ngj@uah.edu iXpressGenes Inc
  3. 3. Disease Target Identification/ Bioinformtics Protein Sequence Structure-based Drug Design Process Protein Production Crystals X-ray/Neutron Crystallography StructureLead Structure Chemoinformatics Biochemical Assays Cell-based Assays Animal Tests Clinical Trials Drug
  4. 4. Structure-based Drug Design Process StructureLead Structure Chemoinformatics Biochemical Assays Cell-based Assays Animal Tests Clinical Trials Drug Experiment Typical cost per compound ($) Computer modeling $10 Biochemical assay $400 Cell culture assay $4,000 Rat acute toxicity $120,000 Animal efficacy trial $300,000 Rat 2-year chronic oral toxcity $800,000 Human clinical trial $500,000,000 Young, D.C. (2009). Computational Drug Design: A guide for computational and medicinal chemists. Wiley & Sons, Inc. Publications
  5. 5. 107,324 As of Thursday 30 June, 2016 <100 Structures determined by neutron diffraction (<0.08% of total)
  6. 6. 50% Of the atoms in a protein are hydrogen and the majority of the proteins do not have structural placement and biological function for hydrogen atoms. The role of hydrogen atoms in protein structures is severely understudied. Why is protein Neutron Crystallography important?????
  7. 7. Munshi et al. (2012). Rapid visualization of hydrogen positions in protein neutron crystallographic structure. Acta Cryst. Section D 68:35-41
  8. 8. Inorganic Pyrophosphatase (IPPase) + IPPase Mg2+ ATP + AMP
  9. 9. Granada crystallization box(GCB) and facility (GCF). Counter diffusion crystallization can be performed in capillary filled with protein solution set to equilibrate with a precipitant that slowly
  10. 10. A B C D E F G 1 2 3 1 2 3
  11. 11. Ground Microgravity A B IPPase + Mg+2 (Acetate) Length of capillary = 70mm; Inner diameter = 2mm Original sample code: 6C
  12. 12. Ground Microgravity A B IPPase + Mg+2 (Acetate) Length of capillary = 70mm; Inner diameter = 2mm Original sample code: 5C
  13. 13. 0.00 5.00 10.00 15.00 20.00 25.00 30.00 35.00 40.00 45.00 1.502.503.504.505.506.507.508.50 I/σ Resolution (Å) B Space Earth
  14. 14. I/σ Resolution (Å) C 0.00 10.00 20.00 30.00 40.00 50.00 60.00 70.00 80.00 1.502.002.503.003.504.004.505.005.50 Space Earth
  15. 15. H2O H2O H2O H2O H2O D2O D2O D2O D2O D2O Ca2+ Ca2+ Tyr56 Tyr56 Lys105 Lys105 H2O H2O H2O H2O H2O D2O D2O D2O D2O D2O Ca2+ Ca2+ Tyr56 Tyr56 Asp71 Glu22 Glu22 Lys105 Glu22 Glu22 Tyr56Lys105 Asp71 Lys35 Lys35 Asp71 Tyr56 8 44 PDB ID: 3Q3L,3Q9MPDB ID: 3Q3L,3R5V
  16. 16. NIH and CASIS Partnership on Microphysiological Systems for Translational Research in Space Danilo A. Tagle, Ph.D. Associate Director for Special Initiatives National Center for Advancing Translational Sciences, NIH
  17. 17. Human Tissues-on-Chips
  18. 18. NIH-CASIS Coordinated Program in Tissue-on-Chips Systems for Translational Research in Space • Goal: NCATS has established a MOU with the Center for the Advancement of Science in Space (CASIS) to deploy and further develop tissue chip technology platforms for biomedical research at the International Space Station (ISS) that will lead to a better understanding of the molecular basis of human disease and/or the effectiveness of diagnostic markers and therapeutic interventions. • Expected outcome: Among the areas of research encouraged in this program is translational research examining the mechanisms that underlie the effects of diseases or conditions associated with bone and cartilage, skeletal muscle, brain, gastrointestinal tract, lung, liver, skin, microvasculature, or other tissues, as well as research designed to improve the translation of existing knowledge of strategies for the prevention and treatment of such diseases or conditions.
  19. 19. NIH-CASIS Coordinated Program in Tissue-on-Chips Systems for Translational Research in Space • Potential impact: Understanding of the effects of microgravity on human organ systems. It could provide better insight into the molecular basis, including epigenome changes, for many human conditions in space and provide information for novel drug targets for use on Earth. • Key Dates: – Estimated Publication Date of Funding Opportunity Announcement: September 2016 – Application Due Date: December 2016 – Earliest Estimated Award Date: July 2017 – Earliest Estimated Project Start Date: August 2017 • http://www.casistissuechip.blogspot.com
  20. 20. W HERE W E’VE BEEN
  21. 21. THE NEAR TERM FUTURE OF THE SPACE INDUSTRY IS LEO COMMERCIALIZATION NASA and other government agencies have been incredible partners to get us to LEO, and will continue to be so as we stay there and push beyond, but it is time we begin finding sustainable business reasons to be on orbit.
  22. 22. FIBER

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