A $7.5 million dollar grant over a five-year period has been awarded to LBL's hematopoiesis research group by the National Institutes of Health. The overall objective of the grant is to gain a better understanding of the membrane that surrounds red blood cells.
Unlike other types of cells in the body, a red cell has no nucleus or cytoplasmic organelles. It is essentially a membrane envelope stuffed with oxygen-binding hemoglobin molecules. This membrane is an elastic-like network of proteins (called the membrane skeleton) that is responsible for maintaining the structural integrity of the cell as it undergoes extensive and repeated shape deformations during its journey through the cardiovascular system.
"The red cell membrane is ideal for studying cell membranes in general because it is such a pure system," says Mohandas Narla, a biophysicist who leads the hematopoiesis research group. "Research that is difficult to do with nucleated cells is much more readily done in red cells."
The red cell membrane is organized as a hexagonal array of structured proteins in which long rod-like spectrin molecules are cross-linked at each end by binding to two other types of proteins: actin, and protein 4.1. These interactions contribute to the membrane's great flexibility. The same proteins are present in a variety of other cells as well, including white cells and platelets.
Says Narla, "Learning what these proteins are doing in the red cell membrane should also tell us what they are doing in the other more complex cells."
In addition to the medical and biological applications, there is also the possibility that red cell membrane research could lead to the development of a new class of materials.
Explains Narla, "The red cell membrane is one of the softest materials known, yet its tensile strength is greater than that of steel. If we can determine how it is put together and learn more about the relationship between its structure and its function, the technology might be used in the production of soft-surface materials."
The five-year NIH grant provides funding for five specific studies. In one of these studies, Narla, working with Ross Coppel of Australia's Melbourne University, will study how the parasite responsible for malaria is able to modify the red cell membrane to its own advantage. This should provide insight into the normal functioning of the cell membrane. Also, says Narla, if the process is understood, perhaps it can be blocked.
In another study, led by molecular biologist John Conboy, the role of protein 4.1 in regulating membrane functions will be characterized. A third study, led by Joel Chasis, an M.D. specializing in hematology, is aimed at understanding the genesis of the red cell membrane by looking at the changes protein 4.1 undergoes during stem cell differentiation. A collaboration between LBL's Edward Rubin, and Stanford University's Stanley Schrier and Mark Scott, will examine the contributions of oxidative damage to the destruction of the cell membrane and the senescence of anemic cells.
A fifth study, which will be led by two researchers from Children's Hospital Medical Center in Oakland -- Franz Kuypers and Bert Lubin -- will also examine the effects of oxidative damage to the membrane. This study, however, will emphasize the repair mechanisms that restore the membrane to normal.
The awarding of a grant this size by NIH to the hematopoiesis group is particularly noteworthy, according to Mina Bissell, the group's divisional director and the coordinator of LBL's Life Sciences research.
Says Bissell: "National laboratories used to have a number of competitive programs in hematopoiesis, but, in the last decade, most of the DOE funding has dwindled. As a result, scientific programs have been at a minimum.
"At LBL, we are indeed fortunate to have scientists of the caliber of Mohan Narla and his colleagues joining LBL, and to have Dr. Narla lead the program."