The science of immunology deals with the biological and biochemical basis of the defense mechanisms protecting the human body when exposed to infectious agents and toxins. Our research group is interested in signal transduction that induces T-cell activation and monocyte differentiation and the effect of altered gravity environments on these intracellular signal transduction processes. Discovering how these signaling pathways control gene expression and cell fate is critical to understanding how leukocytes function.
In collaboration with Dr Augusto Cogoli, we are analyzing gene expression during T-cell activation in microgravity and altered gravity environments. The Leukin experiment, which investigated early T-cell activation, flew on the STS-107 mission in January 2003. Tragically, Columbia and her crew were lost during re-entry at the end of their 16 day mission. In the year following Columbia's loss we have achieved many of the objectives of the Leukin experiment using the random positioning machine (RPM) in Dr Cogoli's laboratory. The RPM subjects cells to a constantly changing g-vector, simulating some of the conditions of free fall experienced in microgravity. Using Gene Arrays we have been able to identify key genes involved in T-cell activation which are altered with RPM treatment.
This experiment will be re-flown in September 2006 to the ISS on the Soyuz in the Kubik incubator. The astronaut in charge of the experiment on International Space station (ISS) is European Astronaut Thomas Reiter.
Download a video on the history of the Leukin experiment here.
The second immune cell of interest is the monocyte. We are investigating the role of protein kinase C (PKC) isoforms, a family of serine/threonine kinases, in the regulation of monocyte cell functions. We will explore the functional consequences of PKC isoform inhibition under microgravity in a future space shuttle experiment, which is under development.
The effect of microgravity on protein kinase C isoform signaling in human monocytes and T-cells
Experiments performed in orbiting spacecraft have shown that mammalian cell function appears to be sensitive to exposure to low gravity or "microgravity" conditions. In diverse cell types, including T-cells and osteoblasts, impairments in cell responsiveness to mitogenic stimulation reduced, growth rate, gene expression and modified cell cycle progression have been observed in microgravity compared to 1. g conditions. Some signal transduction pathways are perturbed in microgravity, in particular protein kinase C. Since signal transduction and cytoskeleton reorganization are events which regulate gene expression in response to growth factors and mitogens, it seems likely that microgravity induced alterations in these signaling pathways may be the cause of subsequent alterations in cell behavior and function.