Maria Spies, PhD

Research project title

Mechanisms of DNA repair and recombination: from single-molecule biochemistry to anticancer drug discovery

Research description

Work in my lab focuses on the molecular machines supporting genetic integrity, DNA recombination and repair. Specifically, we aim to determine how a combination of molecular associations and posttranslational modifications integrates human RAD51 recombinase, RAD52 and BRCA2 recombination mediators, mismatch repair proteins and recombinational DNA helicases into the network of DNA repair pathways in healthy and malignant cells. We utilize a broad spectrum of techniques from biochemical reconstitutions of DNA recombination, repair and replication reactions, to structural and single-molecule analyses of the proteins and enzymes coordinating these reactions. We aim to provide a completely new picture of the coordinated and dynamic nucleoprotein transactions critical for high fidelity DNA repair and replication, to mechanistically dissect and reconstitute in vitro and in singulo these processes, and to identify and rationally target synthetic lethal interactions of their components with other genome caretakers commonly mutated in cancers.

A number of projects are available in the lab and are typically designed with the students’ interest and expertise in mind. The projects ranged from biochemical/biophysical testing of the small-molecule inhibitors of the key DNA repair and recombination enzymes, to biochemical and single-molecule reconstitution of the central events in the DNA repair pathways, and also to structural biology.

Undergraduate minimum qualifications

Strong academic background. Interest in quantitative biochemical/biophysical research. basic molecular biology skills; university level math, physics, chemistry; if taken biochemistry/physical chemistry/biophysics courses will give some advantage, but are not required. Students with strong computer programming skills may choose and will be encouraged to participate in development and/or optimization of data analysis programs.

Undergraduate role

The undergraduate works with a senior grad student or postdoc in the lab first to learn the basics of experimental techniques and the logic behind the experimental design, proper controls and data analysis. By the end of the project period, the student is expected to be able to independently plan and carry out the experiments.