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We are interested in the working mechanism of proteins. We use
crystallography to obtain snapshots of proteins in atomic detail,
to uncover function, such as how one protein activates another. By
combining protein structure analysis with biochemical analyses we
gain insight into protein action. The group is interested in the
signaling processes that regulate DNA function repair, in
particular ubiquitination. We study ubiquitin ligases and
deubiquitinating enzymes that affect the DNA damage response and
the access to DNA, many of which have been linked with cancer.
Understanding the relationship between their structure and function
can be valuable for designing new and effective anti-cancer
Thijn Brummelkamp develops and uses genetic tools to identify
and characterize genes that play important roles in human disease.
Recently, Thijn's group developed a novel genetic model system
based on haploid human cells to enable inactivation of most human
genes. They use this approach in a variety of different projects
for example to search for cancer cell vulnerabilities or to
identify host factors that are hijacked by viruses to enter human
Macromolecular structures are critical for understanding the
function of proteins and their complexes and to evaluate and
develop new drugs. We aim to understand the spatiotemporal control
that protein interactions and small domains within the same protein
exert on the function of proteins, at the level of the molecular
structure and function. Concurrently, the group is developing
methods to help the wider scientific community study macromolecules
more efficiently by X-ray crystallography.
Phospholipids are best known as the major building blocks of
cell membranes, but some lipids play a signaling rather than a
structural role. Our group is interested in nature's simplest
phospholipid, lysophosphatidic acid (LPA), which we discovered as a
lipid growth factor many years ago. Since then, our group has made
substantial progress in unraveling how LPA regulates numerous
biological processes, including cell migration and proliferation.
Our current work focuses on the LPA-producing enzyme autotaxin,
specifically its mechanism of action and role in tumor progression.
Our ultimate goal is to translate new findings on autotaxin-LPA
signaling into more effective anticancer strategies.