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Masters/PhD projects: Imaging the machines that reshape and remake chromosomes

Master’s thesis and PhD projects in several areas at Max Planck Institute of Biochemistry availabe. We hope to recruit students with a background in physics, biochemistry, or a related field, who have a strong interest in dynamic studies of biological processes using structural and single-molecule approaches. Skills in protein biochemistry, programming, and a basic knowledge of kinetic analysis would be ideal, but are not required. Applicants should have a strong desire to pursue a multidisciplinary collaborative project working closely with others. Creative and independent thinking will be key for the successful completion of the projects.

Imaging the macromolecular complexes that reshape and remake chromosomes

Background: The survival of all organisms depends on the faithful duplication and transfer of genetic material from one generation to the next. In cells, this process is performed by large macromolecular complexes, known as replisomes, which couple the unpackaging of parental DNA with the synthesis of new daughter strands. To ensure genome integrity, these sophisticated molecular machines must coordinate events over a broad range of time and length scales, from the breaking and reformation of chemical bonds within DNA polymerases to the large-scale structural rearrangements of chromosomes. We seek to define the operating principles that guide replisome assembly and function on complex cellular substrates. We are particularly interested in understanding how replication overcomes the numerous structurally diverse obstacles frequently encountered on chromosomes.

Methods: We use a combination of structural, biochemical, and imaging techniques to directly visualize the spatial and conformational dynamics of critical replication intermediates. These efforts range from detailed biophysical investigations of individual complexes and interactions to studies of completely reconstituted replisomes in vitro (E. coli, S. Cerevisiae). We use cutting-edge single-molecule imaging approaches that provide high spatial and temporal resolution to study the dynamics of single replisomes.

We are currently offering Master’s thesis and PhD projects in several areas. First, we are developing single-molecule approaches to directly visualize the disassembly and reassembly of nucleosomes during replication. In the context of this project, we are seeking students to work in a team to purify histone chaperones and remodelers and exploit several chemically diverse fluorophore labeling strategies for single-molecule visualization. Second, we are looking for students to help in our studies of replication and transcription conflicts. Of particular interest are rare events were RNA polymerase bypasses replication factors. Finally, for those interested in software development and biophysics, we are developing ultra-high-throughput approaches to hunt for rare but deadly DNA breaks by topoisomerases.

Please get in touch for further details and to hear about other currently offered projects.

Our lab is located at the Max Planck Institute of Biochemistry. You can find us on the web at http://www.biochem.mpg.de/duderstadt and https://duderstadtlab.org