terrestrial life in space€¦ · terrestrial life and microgravity •as life evolved on earth, a...
TRANSCRIPT
Neal R. Pellis, Ph.D.
Director
Division of Space Life Sciences
Universities Space Research Association
Houston, TX 77058
Terrestrial Life in Space What Can We Learn From Cells?
Clinical Problems in Space • 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 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
• 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) – 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
Log10 Gravity
-6 -5 -4 -3 -2 -1 0 1
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Hypo-G Hyper
G
Hypothesis: Relationship Between Gravity and
Biological Activity
Log10 Gravity
-1.0 -0.8 -0.4 -0.6 -0.2 0
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Fractional-G
Mars
-1.2
Earth 25
50
75
100
Moon
Areas of Investigation for Space Exploration
• 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
• Shear
• Mass transfer
• Surface contact
• No sedimentation
Fundamental Questions
• 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)?
14
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?
15
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?
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.
Analog Systems
Isopycnic Solution
(Neutral Buoyancy)
Suborbital Rockets
Parabolic Flight
Superconducting
Magnet Diamagnetic
Magnetic Levitation Solid
Body
Fluid
Rotation
Drop Tower
6o Head Down
Tilt Bedrest
Centrifugation
Hyper G
Unique aspects of mG
• 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
1 G 1 G
m G Changes:
Fluid distribution
Gene expression
Signal transduction
Locomotion
Differentiation
Metabolism
Glycosylation
Theory of the Effect of mG on
Mammalian Cells 1 G m G
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
Changes:
Gene expression
Shift to secondary metabolism
Quorum sensing?
Virulence
Mechano-responsive mechanisms
Replication rates
Biofilm formation
Bacillus
spacecowboyum
1 G 1 G
m G
Theory of the Effect of mG on Bacterial Cells Response of cell with non pliant cell walls
Bacteria
1 G m G
?? 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 baro-
responsive mechanisms leading to the phenotypes seen
in space. May be applicable to plant cells
Cellular Responses to mG • 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
• Programmed cell death
• Cellular movement
• Cellular repair
• Cytokine synthesis and secretion
• Glycosylation
• Differentiation and tissue morphogenesis
• Biofilm formation and deposition
Significance • There is little doubt that cells as representative of
terrestrial life respond to 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:
In 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.