Terrestrial Life in Space
What Can We Learn From Cells?
Neal R. Pellis, Ph.D.
Director
Division of Space Life Sciences
Universities Space Research Association
Houston, TX 77058
pellis@dsls.usra.edu
Clinical Problems in Space
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Visual impairment
Exposure to ionizing radiation
Bone density decrease
Muscle Atrophy
Cardiovascular Deconditioning
Psychosocial impacts
Vestibular Dysfunction
Hematological changes
Immune Dysfunction
Delayed wound healing
Gastrointestinal Distress
Orthostatic Intolerance
Fluid Shifting
Renal stones
Nutrition
Paradigms Lost
• The Earth is the center of the universe
• Blood letting ameliorates most disease
• Accumulations of old rags in the attic
spontaneously generate rats
• Read my lips, no new taxes…
• I never inhaled…
• Humans cannot survive outside the Earth’s
environment
• Cellular and intracellular components are too
insignificant in mass to be affected by the loss
of gravity
"There is a place in your brain, I
think, reserved for 'the melancholy
of relationships past.'
It grows and prospers as life
progresses, forcing you finally,
against your grain, to listen to
country music."
(K.B. Mullis et al., eds., The Polymerase Chain Reaction,
Birkhauser: Boston, 1995, p. 427).
Terrestrial Life and Microgravity
• As life evolved on earth a multiplicity of physical and
chemical factors invoked adaptations and
participated in the complicated selection process
• For many factors there are clear examples of the role
of changing physical forces in evolution
• A notable exception is gravity. It has been constant
for the 4.8 billion years
• Therefore, there is little or no genetic memory of life
responding to force changes in the low gravity range
Why Space Cell Biology?
• As is true for terrestrial based biomedicine,
analysis of the cellular response to microgravity
offers the prospect of elucidating underlying
mechanisms that can be the basis for effective
treatment.
• Observation of the cellular response to variation
in ‘G’ reveals novel adaptive mechanisms.
• Understanding basic cellular mechanisms
necessary for the adaptation of terrestrial life to
low gravity environments
Interactions in Nature
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Gravitational
Electromagnetic
Strong submolecular forces
Weak submolecular forces
Interactions in Nature
• Gravity is the weakest of the four but has a
vast radius of influence
• Among the four, gravity is considered the
sculptor of the universe
• Methods for studying gravitational influences
on biological processes (Microgravity Analogs)
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Theoretical analysis and computer modeling
Changing the weight loading
Hypergravity
Free fall strategies
– Space experiments
An Important Question in Space Biology
The Relationship Between Gravity and Biological Activity
Hyper
G
Known response suites
and relationships
Your favorite
Biological Response
mG
The vast zone of the unknown
-6
-5
-4
-3
-2
-1
Log10 Gravity
0
1
An Important Question in Space Biology
The Relationship Between Gravity and Biological Activity
Hyper
G
Known response suites
and relationships
Your favorite
Biological Response
mG
The vast zone of the unknown
-6
-5
-4
-3
-2
-1
Log10 Gravity
0
1
Hypothesis:
Relationship Between Gravity and Biological Activity
Your favorite
Biological Response
(%of Earth Gravity)
Fractional-G
100
75
50
Moon
Mars
25
-1.2
?
-1.0
-0.8
-0.6
-0.4
Log10 Gravity
Earth
-0.2
0
Areas of Investigation
for Space Exploration
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Basic human physiology
Plant life used for O2 and for food
Bioregenerative microbes
Normal flora
Environmental monitoring
Exploration proes
Areas of Investigation for Applied Science
• Tissue engineering
• Vaccine and drug development
• Models of human disease
• Living reporter sensors
Fundamental Questions
• What is the basis of the cellular response to
microgravity?
– Intrinsic response in the cell (gravisensor?)
– Cellular response to environmental changes induced by
gravity
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Shear
Mass transfer
Surface contact
No sedimentation
• How is response different in microbial cells (that are
bound by a cell wall) vs. eukaryotic/mammalian cells
that do not have a cell wall?
• How do changes in individual cells relate to tissues,
organs, and organisms?
• How does microgravity change cell response
thresholds to other stimuli (radiation, magnetic fields,
shear, toxins, other chemicals)?
Scientific Questions to Address
• Adaptive responses of cells to
microgravity and to the space
environment?
• Phenotypic and genotypic changes
induced by microgravity, space, and
planetary environments?
• Does the space environment invoke a
selective pressure on replicating cells?
• How much ‘G’ is required to maintain
normal function?
• What new cell biology applications can be
achieved in low gravity environments?
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Practical Questions
• How do changes in individual cells relate to
tissues, organs, and organisms?
• How does microgravity change cell response
thresholds to other stimuli (radiation, magnetic
fields, shear, toxins, other chemicals)?
• Can we use cells to conduct missions with
unknown consequences?
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Analog Systems
To investigate the cellular and tissue responses to microgravity
it was essential to design systems that approximate the some of the
microgravity conditions and provide the opportunity to study these
phenomena on Earth in a more controlled and available venue.
6o Head Down
Tilt Bedrest
Drop Tower
Isopycnic Solution
(Neutral Buoyancy)
Suborbital Rockets
Parabolic Flight
Centrifugation
Hyper G
Magnetic Levitation
Solid
Body
Fluid
Rotation
Superconducting
Magnet
Diamagnetic
Unique aspects of mG
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No sedimentation
Loss of gravity driven convection
Decreased hydrodynamic shear
No hydrostatic pressure
Mass transfer is limited to the rate of
diffusion
Animal Cells in Space
mG
Changes:
1G
fluid distribution
gene expression
signal transduction
locomotion
differentiation
Metabolism
glycosylation
1G
Theory of the Effect of mG on
Mammalian Cells
m
G
1G
Potential Change in membrane:
Structure
Composition
Bileaflet organization
Lipid rafts
Association with the cytoskeleton
Perhaps the ‘forced’ shape change induces a
cascade of responses otherwise unrelated to mG
Bacteria in Space
mG
Changes:
Bacillus spacecowboyum
1G
Gene expression
Shift to secondary metabolism
Quorum sensing?
Virulence
Mechano-responsive mechanisms
Replication rates
Biofilm formation
1G
Theory of the Effect of mG on Bacterial Cells
Response of cell with non pliant cell walls
Bacteria
1G
mG
?? Pin<<Pout??
In bacteria, the cell wall is a rigid structure that surrounds
the cell membrane. Perhaps the decrease in gravity
accentuates the attractive forces between fatty acid side
chains of triglycerides resulting in outward force on the
wall. This in turn activates mechano- and baroresponsive mechanisms leading to the phenotypes seen
in space
May be applicable to plant cells
Cellular Responses to mG
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Signal transduction
Shape change
Gene expression
DNA damage
Cell division rates
Orientation of subcellular components
– Changes in nucleoli morphology
– Synthesis and orientation of macromolecules
– Cytoskeleton
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Programmed cell death
Cellular movement
Cellular repair
Cytokine synthesis and secretion
Glycosylation
Differentiation and tissue morphogenesis
Biofilm formation and deposition
Physical Factors to Consider
in Experimental Design
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Gravity
Mechanical impacts
Hydrodynamic shear
Convection
Vibration
Radiation
Barometric Pressure
Hydrostatic pressure gradients
Significance
•There is little doubt that cells as representative of terrestrial life
respond decreased gravity environments.
•The mechanism of gravity induced responses in cells is
unknown.
•Nevertheless, microgravity affords a unique tool to probe the
underlying mechanisms in life systems at the cellular and
organismal level.
•We plan use of this tool
• novel ways to increase our understanding of the role of
gravity in life processes
• to achieve goals in applied biological science and
technology development
• to elucidate the long term effects of microgravity on
terrestrial life by using cells as explorers
Obstacles in Colonizing Space
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Financial
Political and philosophical
Propulsion
Dealing with the reality that it could be a
multi-generational mission
• Managing health
• Managing the logistics
• Decreasing the energy requirements for
life?
We are going to have to learn by
exploring the Solar System
• Candidates for colonization are:
– The Moon
– Mars
• Candidates for exploration
– Europa (Moon of Jupiter)
– Titan (Moon of Saturn)
– Encelaedus (Moon of Saturn)