UC San Diego

In recent years, we have seen the advent of high-throughput sequencing technologies, providing us with the unprecedented ability to query DNA, RNA, and proteins.

We have witnessed the vast variability of molecules at the level of sequences. Disentangling this molecular variability, and describing the array of changes to molecules, is critical to understanding certain biological processes. This dissertation asks questions about certain functions, e.g., immune response and N-terminal events, and attempts to ascertain any patterns in the data.

While the N-terminus may seem like an innocuous portion of translated proteins, it in fact, harbors great variability. Despite all proteins starting with a methionine (Met), many lose this first residue, to N-terminal methionine excision (NME), exposing the second residue. Additionally, some proteins gain an acetyl group to the N-terminus. These N-terminal post-translational modifications (PTMs) make up the N-terminome.

Another biological process that introduces variability is that of the immune repertoire. B-cells, responding to an antigen, produce heavy and light chain proteins to form an antibody. These antibodies are comprised of three gene-segments, termed V, D, and J. Unlike typical exonic splicing events, VDJ somatic recombination occurs at the genomic level within B-cells. Additionally, somatic hypermutation (SHM) introduces a very large number of mutations. Thus, the population of B-cells will produce a large variety of antibody heavy and light chains, in an attempt to target an antigen. This immunoglobulin repertoire forms part of the immunome that we attempt to characterize in different projects.