Laboratory of Protein and Nucleic Acid Chemistry

Our overarching goal is to understand DNA replication and protein translation at the molecular level.  In our research lab in the Chemistry Department at Ben-Gurion University of the Negev we are utilizing innovative biophysical tools and approaches to assess the structural nature and the biomolecular interactions in protein-protein and protein-nucleic acid complexes, and, in turn, we learn how these interactions determine and impact biological catalysis of these domains of life.  Our interdisciplinary approach, spanning and integrating chemistry and biology, employs a wide range of techniques.

BASIC RESEARCH

DNA replication has been studied extensively in many model organisms, the organization of the protein components at the replication fork of M. tuberculosis, and their activities are poorly understood. Understanding the fundamental mechanisms that regulate DNA replication in M. tuberculosisis is critical for developing new therapeutic approaches to control bacterial proliferation. To date, the minimal M. tuberculosis replisome arrangement that is required for coordinated DNA synthesis is not known, and the role that many protein components play at the replication fork, as well as the interactions between them, are still largely unexplored. Mounting evidence collected over the past few years supports the idea that DNA replication in mycobacteria is unique and maybe coordinated differently from that found in other bacteria and humans.

In filling these knowledge gaps, my lab aims to shed light on the activities at the replication fork of M. tuberculosis. In particular, we will unravel the sequence on the DNA recognized by the DnaG primase, an essential enzyme that binds to a specific sequence on the genome and performs catalytic activity necessary for normal DNA replication. Revealing the primase binding signature on genomic DNA was made possible through protein-DNA binding microarray containing a massive amount of DNA sequences with their assigned binding scores to the primase (A. Afek and S. Ilic et al., 2019 iScience). We then sought to leverage advances in data science and machine learning to analyze DNA-primase interactions (A. Soffer et al., 2020, 2020, Nucleic Acid Research). Machine-learning algorithms were used to characterize specific DNA sequences that lead to DNA sequence recognition which is an essential step in the recruitment of DNA polymerase on the DNA replication fork.

APPLIED RESEARCH

The imminent need for the development of new antibacterial drugs will lead us to develop inhibitors targeted against components in central molecular biology domains in a bacterial cell, such as DNA replication and protein translation.