These pages will chronicle the travels and travails of Dr. Millie Hughes-Fulford and her research team from San Francisco,

to Moscow,

to Baikonour,













and finally, putting an experiment on board the International Space Station.

(Image courtesy of NASA.)

The Project: To determine what happens inside T cells in zero gravity that makes them less able to respond to infection.

The Mission: To launch human T cells on board a Russian Soyuz. Destination: International Space Station.

We will travel from San Francisco to Moscow where we will meet with our European collaborators and others from the European Space Agency. Together, we will be escorted by Russian military convoy to the Cosmodrome in Baikonour, Kazakhstan. We will prepare T cells from human blood that will board the Russian Soyuz spacecraft and be launched into space. Thomas Reiter, the newest astronaut to join the crew of the International Space Station (ISS), will activate the T cells on board the ISS. He will prepare RNA from the T cells which contain genetic messages corresponding to the genes that are turned on during activation. These samples will be brought back on the Soyuz in 4 days to where we will be waiting in Moscow. Then, with a lot of explaining to both Russian and American customs officers, I'm sure, we will attempt to bring these samples back to San Francisco for analysis.

The Why:

The immune system, which is our bodies' defense against infections, is weakened in astronauts who travel in space. T cells, an important component of the immune system, do not respond properly to stimulation when there's no gravity. We must figure out what is going on with T cells in space in order to keep astronauts safe and healthy for longer space journeys to the Moon and Mars.

The Background:

Since the time of the Apollo missions, astronauts have been coming back from spaceflight with depressed immune systems. Fifteen of 29 (52%) Apollo astronauts had bacterial or viral infections during, immediately after, or within 1 week of returning to Earth. One astronaut was infected with an opportunistic pathogen, Pseudomonas aeruginosa, that rarely causes disease in people with normal immune systems. Because of these observations, NASA implemented a preflight quarantine policy to reduce the incidence of infections during and after spaceflight (Hawkins, 1975, please see references).

T cells are critical cells in the immune system that orchestrate the immune response. The first spaceflight experiments of T cells showed that proliferation of activated T cells in space was only 3% of what normally occurs in activated T cells on Earth (Cogoli, 1984). Growing T cells in random positioning machines on Earth that simulate zero gravity, researchers found that T cells in zero-g produce reduced levels of interleukin-2 (IL-2) and activated interleukin-2 receptor (IL-2R alpha) (Walther, 1998). IL-2 is a protein secreted by T cells that, when bound to its receptor also on T cells, activates T cells and causes proliferation. In addition to IL-2 and IL-2 receptor, the expression of around 90 other genes in T cells are inhibited in conditions of simulated zero-g. Many of these genes are important in transducing signals within the cell that lead to activation (Booyaratanakornkit, 2005).

The return of T cells to spaceflight with our experiment will verify the findings of those previous ground-based experiments in true zero gravity. We will analyze the expression of nearly 9,000 different genes in T cells activated in space using gene chip technology. This data will allow us to confirm whether the genes we suspect to be inhibited by zero gravity are really turned off in space as well as identify new genes that may be involved in the T cells' lack of activation in space.

The Now:

The Space Shuttle Discovery just launched into space on July 4th, 2006. The shuttle will bring Thomas Reiter, the European astronaut trained to perform our experiment, to the International Space Station (ISS). Reiter will be the 3rd and newest member of the crew on board the ISS. He plans to stay up there for about 6 months. Our experiment will go up on the Soyuz to meet him in September.

As for us.... We are performing several run-throughs of mock experiments to make sure that everything will go as smoothly as possible when we have to do the real deal in Baikonour. We are making a list of things to pack: from antibodies to pipette tips. And, we are trying to sort out our Russian visas (no small feat!)

The adventure begins.....

Look up in the night sky. There's science going on up there.

Want to know more?

Try these websites:

www.NASA.gov - Look up the latest on the Discovery shuttle mission and what's up on board the ISS.

www.ESA.int - The European Space Agency portal. Check out the bio on our astronaut, Thomas Reiter.

www.russianspaceweb.com - Learn about the history of the Russian space program and what a Soyuz looks like.

www.niaid.nih.gov/final/immun/immun.htm - Want more on the immune system? Here's a nice primer from the National Institutes of Health.

http://quest.nasa.gov/projects/flies/index.html - There's a whole lot of immunology going on in space these days. Here's a fun site from NASA who has got fruit flies, Drosophila melanogaster, on board the Discovery Shuttle. Fruit flies have an "innate immune system" with some similarities to humans. Find out what NASA scientists are doing with "Flies in Space." (There's also a colorful background section on the immune system.)

www.labofcellgrowth.com - This is our lab's website. Learn about our T cell experiment in more detail as well as other projects in the lab. Get to know who we are. Millie, the boss, was a astronaut herself and flew the first Spacelab mission dedicated to biomedical studies!

If you want the nitty-gritty on T cells in space,

check out these references:

Hawkins, W., and Zieglschmid, J. (1975) Clinical aspects of crew health. In Biomedical results of Apollo (Johnston, R., Dietlein, L., and Berry, C., eds) pp. 43-81, NASA, Washington, DC.

Cogoli, A., Tschopp, A., Fuchs-Bislin, P. (1984) Cell Sensitivity to Gravity. Science 225, 228-230.

Walther, I., Pippia, P., Meloni M.A., Turrini, F., Mannu, F., Cogoli A. (1998) Simulated microgravity inhibits the genetic expression of interleukin-2 and its receptor in mitogen-activated T lymphocytes. FEBS Lett. 436, 115-118.

Boonyaratanakornkit, J.B., Cogoli, A., Li, C.-F., Schopper, T., Pippia, P., Galleri, G., Meloni, M.A., Hughes-Fulford, M. (2005) Key gravity-sensitive signaling pathways drive T-cell activation. FASEB J. 19: 2020-2.