Dr. Berhane Ghebrehiwet, Professor of Medicine and Pathology, Department of Medicine, discusses the work of Intel finalist Nithin Tumma
Nithin Tumma's strength and thrill was computational biology. Therefore when he came to work in my laboratory, I challenged him with the task of identifying the structural domains on gC1qR, (a molecule our laboratory has been working on for a number of years) that allow it to interact with a plethora of pathogenic ligands including an HIV-1 protein called gp41. Using the known crystal structure of gC1qR, Nithin used in silico computational analysis to identify the precise gp41 binding site on gC1qR. The relevance of this discovery is as follows. During the first phase of HIV infection, the immune system is broken down because CD4+ T cells are killed due to viral load. However, during the second phase of HIV pathogenesis, it is not the infected cells that are destroyed, but rather the uninfected DCD4+ cells. The mechanism of this was not known until recently. During the late phase of HIV infection, gp41 released from the virus, binds to gC1qR on CD4+ T cells to induce the expression of a "death signal" called NKp44L. This "death" molecule in turn is recognized by Natural Killer or NK cells through which they destroy the uninfected, NKp44 expressing CD4+ cells. Because molecules that inhibit the interaction between gp41 and gC1qR can potentially prevent the expression of NKp44, this observation may in the log term, lead to the development of peptide-based or antibody-based therapeutic modalities.