Experiment SPC [Soluble Protein crystallization]

read about Dr. Vaughan Oosthuizen

The human body’s immune system protects us against infectious organisms such as viruses, bacteria and parasites. In the human body we find protein molecules, called antibodies. These antibodies are the policemen of the body that patrol the body looking for these dangerous infectious organisms. Once these antibodies find an infectious agent, they “tag” them so that cells in your body can destroy the infectious organism. An important part of this process is the recognition by these immune cells that there is a danger. This recognition is achieved by another set of protein molecules belonging to the immune cells, that act as receptors, molecules that dock with the antibody “tags”, much the way that ships dock in a harbour, or a space craft docks with a space station.

Some infectious organisms, however, are clever enough to block this docking process, one such example is HIV. Today scientists are learning more about how this docking process works, so that we can design medicines that will work at the level of this docking step. For scientists to learn about how antibody “tags” dock with immune cells, we use an experiment called X-ray crystallography to show us how the atoms of each protein molecule interact with each other.

Crystals of proteins can be made by having two liquids, one containing the protein, the other containing a substance that absorbs water from the protein, slowly causing the protein to crystallize [see photograph of crystallization device]. If these protein crystals are then exposed to X-rays, the atoms of the protein diffract the X-rays into a specific pattern. From this pattern, scientists can trace the position of the atoms in the protein and so learn how the proteins interact with each other.

Once we know how the proteins interact, we can design medicines that promote or block the docking process. In allergies and immune diseases for example, it may be beneficial to block the docking process.

On his mission with Soyuz at the International Space Station, Mark will try to make crystals of two such “docking” proteins. One of the docking proteins is involved in many allergies, the second with HIV infections. We will place the proteins and their precipitant solutions in a crystallization device (photograph) here on earth. The device is sealed and taken to the ISS, where Mark will start the crystal growth by opening the seal. This allows the protein to “dry” and form a crystal. Normally the process is a slow one, so if crystals form they will only return to earth on later missions. The microgravity conditions in space sometimes allow bigger and better crystals to be made than we can make here on earth, because the protein “dries” at a slower rate. If better crystals are made in space, we will then analyse these crystals and at a later stage design medicines that can protect humans from viruses, bacteria and allergic or autoimmune conditions.

South Africa stands to benefit greatly because of the high levels of HIV infection and AIDS in this country, but the fields of immunology, pharmacology and biochemistry on the global level will also obtain valuable information if we are successful.

Benefits of research to South Africa

The human immune system uses immunoglobulin receptor proteins (FcR) found on the surface of all immune competent cells to recognize pathogenic organisms that have been bound by immunoglobulin proteins. This recognition system is essential for successful destruction of pathogens that infect humans. When errors occur in this recognition system, allergic and autoimmune diseases can develop, infections may persist and cancers can arise. These reactions ensure an efficient and broad immune response by triggering endocytosis of immune complexes, regulating antibody production by B-lymphocytes, as well as antibody-dependent cell-mediated cytotoxicity and release of inflammatory mediators that activate other immune cells. Many pathogens however, have developed mechanisms that evade this recognition process, often by interfering with binding between FcR and immunoglobulins. Some examples of this are HIV (1), ebola (2), measles (3), and dengue (4). Since the South African MRC as the greatest medical threat facing this country currently regards HIV, many avenues are being investigated to deal with the pandemic. Being at the centre of both cellular and humoral immune responses the FcR is an ideal target for immunotherapy.

However, immune therapies that work at the level of FcR require knowledge of the structure of these proteins. One of the best methods of solving protein structures is by X-ray crystallography, and there are cases where crystal growth of proteins under microgravity produces protein crystals of superior quality to those produced on earth. The proposal to crystallize two FcR proteins, one involved in HIV infection (FcyR) and the other involved in controlling many allergies (Fc&RII) is clearly of benefit to South African science. Immediate benefits would obviously be gained from using a high profile mission to show the global impact and quality of South African research. Benefits of a long-term nature would include development of immune therapies that could potentially be used in alleviating the South African AIDS crises, based on the information obtained from successfully solving the structure of these two proteins.