New Chemical Tools to Study Postranslational Networks
Posttranslational modifications (PTMs) are important events that lead to defined changes in protein function. Because these modifications occur after translation, they can be difficult to understand based on the genetic template, and are often part of complex posttranslational networks. Our lab is focused on the innovation of chemical methods that can be used to understand the biology of two such PTMs: nitration/nitrosylation and ubiquitination. In the first case, we exploit the unique reactivity of nitric oxide (NO)-derived PTMs to develop new chemistry that can be used to detect proteins modified by NO in live cells. In the second case, we use existing chemical biology methods to develop a one-of-a-kind strategy that can track ubiquitin as it moves through its sequential, multi-enzyme cascade to become linked to a target protein in live cells. In both cases, the developed chemistry will be used to address longstanding questions about the role of these vital, yet elusive, PTMs in innate immunity, inflammation, autoimmune disease, and cancer.
Non-enzymatic PTMs for Chemical and Synthetic Biology
Most chemistry that occurs within the cell is controlled by enzymes, yet there are several non-enzymatic PTMs that are observed to occur with selectivity in nature. Our lab is interested in understanding the molecular basis for non-enzymatic reactivity in biological systems. In particular, we aim to identify how the local environment on a protein surface influences non-enzymatic reactivity and selectivity. We address this question in two ways: 1) We explore a natural non-enzymatic PTM in order to identify the features of local environment--particularly primary sequence--that lead to enhanced reactivity. 2) We employ engineered organocatalytic peptides to develop new bioorthogonal reactions. This chemistry reports on changes in local environment, especially those involving transitions in tertiary structure. This work will expand the range of non-enzymatic chemistry that can be harnessed to provide valuable chemical and synthetic biology tools.
Apply to the Sackler School
The priority application deadlines are as follows:
December 1: Basic Science Division PhD Programs
February 15: Building Diversity in Biomedical Sciences
March 31: Post-Baccalaureate Research Program
May 1: Clinical & Translational Science, MS in Pharmacology & Drug Development
June 15: Online Certificate in Fundamentals of Clinical Care Research