My research probes the structure and function of proteins, especially proteins associated with membranes. My two areas of interest are:
A. Chemical signals that induce growth and development (or death) in the nervous system.
The key communication cells in the nervous system are nerve cells. The functional integrity of a nerve cell is dependent upon helper cells (called glial cells) which surround the nerve cell and protect and nourish it. Many factors (some chemicals and also proteins known as growth factors) are involved in signaling the onset of development of the nervous system and the onset of recovery from damage to the nervous system. Other factors are involved in cell death. These factors bind to membrane proteins called receptors and induce intracellular changes. The groups of proteins and chemicals responsible for the intracellular changes are called second messenger systems.
All the neurochemistry research projects are joint projects with the laboratory of Dr. Jun Yoshino. Some of the components of the second messenger systems that we are currently investigating are listed below:
- Nitric oxide is a very short-lived messenger which is made intracellularly by the enzyme nitric oxide synthase (NOS). Nitric oxide is already known to play a role in some neuronal transmission, in vasodilation, and in host response to infection. Does it play a role in signaling the onset of nervous system repair after tissue damage? Some preliminary data have indicated that some of the chemicals associated with cellular growth and with damage do cause an increase in nitric oxide production.
- Ceramide is a compound involved in lipid metabolism. An inhibitor of a specific enzyme in a lipid biosynthesis pathway has been shown to cause a rise in ceramide concentrations and also inhibit cell growth (and cause cell death?).
- Prostaglandins are also second messengers in the nervous system and their production may be coordinated with the production of a ceramide.
- Glial growth factor (GGF) is one of a few growth factors which can induce the repair of glial cells (Schwann cells) in the peripheral nervous system. It also appears to play a major role in embryonic nervous system development. In his senior research, Kevin Duwe found that GGF acts on Schwann cells by changing the intracellular pH. A certain second messenger system is implicated, but its role is not yet proven. In another collaborative project, research using more specific inhibitors of the suspected second messenger is needed.
B. Organization of the proteins which capture light in photosynthesis (light harvesting proteins). This project is an extension of my long-term interest in the light harvesting proteins. All chlorophyll involved in photosynthesis is bound by proteins. We are using chemical modifications to probe the nature of the protein-protein interactions in the large multiprotein complex (possibly 24 proteins) that forms in the membrane where photosynthesis occurs. Small complexes of the proteins are isolated and their ability to associate with each other is studied. We are investigating how chemical changes on the surface of the proteins affect their association with each other.
Students involved in these research projects will learn some of the basic biochemical techniques used in protein chemistry and membrane chemistry. Centrifugation and protein separation techniques (gel electrophoresis, gel filtration chromatography, high pressure liquid chromatography) are used to purify proteins and prepare membrane fragments. Please feel free to drop by my office to obtain further information about these projects or to discuss other research ideas.