NSF Postdoctoral Fellowships in Biology combine research and training components to prepare young scientists for careers in biology; those in the International track provide them an opportunity to establish international collaborations and take advantage of research facilities and opportunities abroad. Forging strong international collaborations is mutually beneficial to the U.S. and the foreign hosts. The Fellows are expected to be leaders of the nation's scientific workforce of the future. This fellowship to Mehrnoosh Arrar supports a research and training plan entitled "Structural basis of signal sensing and transmission in bacteria." The host institutions for this fellowship are the University of Buenos Aires and the Leloir Research Institute, and the sponsoring scientists are Professors Dario Estrin, Marcelo Marti, and Fernando Goldbaum.
The goal of the proposed research is to understand, mechanistically, how a stimulus that binds to one terminus of a biomolecular sensor induces the necessary conformational changes in the opposite and distant terminus, consequentially activating a signal cascade within the cell. The motivation for understanding the physical basis of the sensing machinery is two-fold: (1) to guide the discovery of novel antibiotics through the inhibition of bacterial sensors, and (2) to promote the innovation of engineered molecular sensors by tweaking those already found in nature. The two sensors at the focus of the proposed research are critical in the survival of the bacterium Brucella abortus. B. abortus is the causative agent of a zoonosis called brucellosis, a disease transmitted from cattle to humans through the consumption of infected dairy products. Understanding the molecular machinery that promotes pathogenesis of B. abortus will be critical in the design of effective antibiotics for brucellosis. Novel therapeutics against brucellosis are also of broader interest in terms of national security due to the potential, and historical, use of B. abortus as an agent of biological warfare since it is a bacterium easily transmitted in aerosols.
