Anna laser
Film blue
Nuclei DNA
Tethered DNA

Why do we study genome maintenance?

An awe-inspiring feature of living systems is their ability to rapidly and faithfully duplicate vast amounts of genetic information in preparation for cell division. DNA replication and repair are carried out by a large cadre of specialized molecular machines, and our curiosity drives us to understand the intricate mechanisms by which they function. Moreover, defects in replication and repair cause varied human diseases such as cancer, bone marrow failure, and neurodegeneration; uncovering how the genome is maintained in healthy cells and how this process fails in human disease lays the foundation for new therapeutic interventions.

Why use Xenopus egg extracts?

Egg extracts of the African frog Xenopus laevis (our vertebrate relative) contain the entire frog proteome and support virtually all aspects of genome maintenance. The extracts efficiently replicate added plasmids, including ones containing DNA damage, revealing how the replication machinery overcomes DNA lesions in the template strands. The added plasmids undergo chromatinization, and replication and repair are regulated by kinase and ubiquitin signaling, as seen in cells. We have used this system not only to elucidate the mechanisms of known processes, but also to discover previously unknown DNA repair pathways that are mutated in cancer (see Research). Single molecule imaging allows us to visualize critical intermediates of replication and repair in a physiological environment. In short, Xenopus egg extracts represent a “cell in a test tube” that allows mechanism- and discovery-based approaches in a physiological setting.

Why join the Walter laboratory?

The Walter laboratory is a welcoming and highly interactive environment. Post-doctoral fellows and graduate students share reagents, expertise, and ideas to reach their common goal of understanding how cells replicate and repair DNA and how these processes go awry in human disease. We are always looking for energetic pre-doctoral students and accomplished post-doctoral fellows with expertise in molecular biology, biochemistry, and/or single molecule imaging. Prior knowledge of Xenopus egg extracts is not required as incoming students and post-docs are trained in all relevant methods by current trainees. Walter lab alumni are successful in obtaining post-doctoral, industry, group leader, and other positions (see alumni).

Read on to learn more about current people and projects in the Walter lab.