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.
Large-volume protein crystal growth
for neutron macromolecular
crystallography
Joseph D. Ng
University of Alabama
in Huntsville
ngj@uah.edu
iXpressGenes Inc

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.
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.
107,324
As of Thursday 30 June, 2016
<100 Structures determined by
neutron diffraction (<0.08% of total)

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.
Munshi et al. (2012). Rapid visualization of hydrogen positions in protein
neutron crystallographic structure. Acta Cryst. Section D 68:35-41

8.
Inorganic Pyrophosphatase (IPPase)
+
IPPase
Mg2+
ATP
+
AMP

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.
A B C D
E
F G
1 2
3
1 2 3

11.
Ground Microgravity
A
B
IPPase + Mg+2 (Acetate)
Length of capillary = 70mm; Inner diameter = 2mm
Original sample code: 6C

12.
Ground Microgravity
A
B
IPPase + Mg+2 (Acetate)
Length of capillary = 70mm; Inner diameter = 2mm
Original sample code: 5C

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.
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.
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.
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.
Human Tissues-on-Chips

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.
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.
W HERE W E’VE BEEN

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.
FIBER