Immunologist Leonid Pobezinsky, veterinary and animal sciences, recently received a five-year, $2.7 million grant from the NIH’s National Institute for Allergy and Infectious Diseases to study specialized microRNA and T-cells. He and his colleagues plan to take a very specific and narrow approach to exploring the possible role of the small non-coding ribonucleic acid (RNA) known as let-7 microRNA in fine-tuning the immune system’s balance of T-cell survival and function.
He explains, “T-cells are generated in childhood before puberty and we keep them for the rest of our lives, so their long-term survival and ability to proliferate is critical. Sometimes they may die and the body needs to replenish the pool, so they can divide very slowly to keep the balance throughout life.”
“But once infection hits, pathogen specific T-cells drastically expand and differentiate into functionally competent effector lymphocytes,” he adds, “and we know that without let-7 microRNA, T-cells cannot survive; this little microRNA is extremely critical for their survival. With this study, we want to know the molecular mechanism that regulate production of let-7 molecules and what other downstream genes let-7 may regulate.”
“That will allow us to discover new genes that control T-cell maintenance. This might allow better survival of effector T-cells in pathological conditions, such as with aggressive tumors and chronic infections,” he points out.
A second phase of the research plan will be to investigate T-cells in action, “not just their survival but when they are activated in order to eliminate pathogen or tumor cells,” the immunologist says. “We suspect that let-7 microRNA regulates how T-lymphocytes differentiate, whether they turn into killers, how memory T-cells remember vaccines, for example, and whether let-7 boosts the immune responses. We’re very excited to understand all these functions.”
Pobezinsky will collaborate with his wife, research assistant professor Elena Pobezinskaya, associate professor Eric Strieter, chemistry, an expert in protein homeostasis, and assistant professor of biology Courtney Babbitt, an expert in quantitative biology and big data analysis. Together they will explore the molecular mechanisms of let-7 mediated regulation of the immune responses.