Investigating the mechanism of meiotic recombination using single-molecule imaging

Key information

Application close date
07 February 2023, 11:59 GMT
Hours per week
36 (full time)
Application guidance
Posted 20 December 2022

Research topics

Chemical Biology & High Throughput Imaging
Background texture taken from the lab imagery.

This is a summer student position supervised by Roopesh Anand in Simon Boulton's lab.

Introduction to the Science

The phenotypic uniqueness of everyone in any population stems from the genetic diversity at the cellular level. The process of meiotic homologous recombination (HR), where DNA segments are physically exchanged between homologous chromosomes, is one of the main two mechanisms responsible for producing genetic diversity. The meiotic recombination requires precise coordination and choreography of numerous proteins involved in this process.

About the Project

In this project, we will be investigating the initial step of meiotic HR known as DNA strand exchange (SE). As the name implies, recombination proteins like DMC1 and RAD51 initiate the process of physically exchanging DNA between homologous chromosomes via SE. Many additional proteins known as recombination mediators help in this process. We will be studying how this process mechanistically occurs, including the role of mediator proteins using bulk biochemistry and single-molecule imaging. Importantly, the analysis of SE mechanism at single DNA/protein molecule level will uncover this process in unprecedented detail. As part of this project, you will learn the processes of protein purification, bulk biochemical analysis techniques and single-molecule experiments. You will also learn the process of preparing various DNA substrates used during these experiments.       

About You 

This project would particularly suit a student studying biochemistry, molecular biology or biophysics, who is interested in understanding the detailed mechanism of biological systems. The DBS Repair Metabolism group is interested in all aspects of DNA damage repair and genomic instability, so this would be a good project for anyone interested in working in this field.

References

1.         Zickler, D. and Kleckner, N. (2015)

            Recombination, pairing, and synapsis of homologs during meiosis.

            Cold Spring Harbor Perspectives in Biology 7: a016626. PubMed abstract

2.         Crickard, J.B. and Greene, E.C. (2018)

            The biochemistry of early meiotic recombination intermediates.

            Cell Cycle 17: 2520-2530. PubMed abstract