Thijn Brummelkamp Group

Experimental biomedical genetics

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Our Focus

Our group uses genetics in haploid human cells to construct a genetic wiring map for human cells and to study important outstanding questions in cell biology. To achieve this, we measure quantitative cellular traits in haploid cells carrying a gene-disruptive mutation and apply sequencing to link millions of mutations in parallel to cellular phenotypes.  

  

Whereas interesting findings can be derived from individual experiments, we have assigned genetic regulators to >160 quantitative phenotypes enabling comparative analysis. These comparisons point out specific regulators that affect only a limited number of traits and broad genetic regulators affecting many traits and can be used to cluster genes with similar phenotypic output.  

  

Next to a loss-of-function approach we have also studied a compendium of cellular phenotypes using a recently developed gain-of- function approach. Using both methods, we have recently identified new biological processes that we are characterizing further: new pathway for the synthesis of triglycerides, a p53-independent pathway for the induction of apoptosis by DNA damage, a new pathway for cellular iron uptake and a new co-activator complex that activates a large series of developmental transcription factors.  

About Thijn Brummelkamp

My Research

Thijn Brummelkamp received his Msc in biology from the Free University in Amsterdam, in 1998. He did his graduate research at The Netherlands Cancer Institute in the laboratory of René Bernards and received his PhD cum laude from Utrecht University in 2003. After his PhD he was appointed as group leader (Whitehead Fellow) at the Whitehead Institute for Biomedical Research in Cambridge, USA. In 2011 his laboratory moved to the Netherlands Cancer Institute in Amsterdam and he became adjunct PI at Center for Molecular Medicine (CeMM) in Vienna. Thijn has co-founded the biotech companies Haplogen GmbH (Vienna) and Scenic Biotech (Amsterdam).

He developed and applied technologies for genetics in cultured human cells (shRNA libraries and genetics in haploid mammalian cells) that are widely used in biomedical research. He identified a new class of intracellular receptors for highly pathogenic Ebola and Lassa viruses, studied the principles of synthetic lethal interactions in human cells, identified genes needed for glycosylation of alpha-dystroglycan and mutated in Walker-Warburg syndrome and assigned a function to the cylindromatosis tumor suppressor gene.

Awards
  • 2015: Ammodo Award, Dutch Academy of Sciences (KNAW)

  • 2013: EMBO Gold Medal

  • 2012: Phoenix Pharmazie Wissenschaftspreis

  • 2012: The Molecular Biosystems Early Career Award

  • 2006: Kimmel Scholar Award, Sidney Kimmel Foundation for Cancer Research

  • 2005: TR35: Elected as one of the world’s top young innovators by Technology Review Magazine

  • 2004: NVBMB Award (Dutch association for biochemistry and molecular biology)

  • 2003: Antoni Van Leeuwenhoek Award, for contributions on Functional Genomics

Key Publications
  1. Blomen, V. A., Májek, P., Jae, L. T., Bigenzahn, J. W., Nieuwenhuis, J., Staring, J., ... & Marceau, C. (2015). Gene essentiality and synthetic lethality in haploid human cells. Science350(6264), 1092-1096.

  2. Brockmann, M., Blomen, V. A., Nieuwenhuis, J., Stickel, E., Raaben, M., Bleijerveld, O. B., ... & Brummelkamp, T. R. (2017). Genetic wiring maps of single-cell protein states reveal an off-switch for GPCR signalling. Nature546(7657), 307.

  3. Carette, J. E., Raaben, M., Wong, A. C., Herbert, A. S., Obernosterer, G., Mulherkar, N., ... & Dal Cin, P. (2011). Ebola virus entry requires the cholesterol transporter Niemann–Pick C1. Nature477(7364), 340.

  4. Nieuwenhuis, J., Adamopoulos, A., Bleijerveld, O. B., Mazouzi, A., Stickel, E., Celie, P., ... & Brummelkamp, T. R. (2017). Vasohibins encode tubulin detyrosinating activity. Science, eaao5676.

  5. Staring, J., von Castelmur, E., Blomen, V. A., van den Hengel, L. G., Brockmann, M., Baggen, J., ... & Perrakis, A. (2017). PLA2G16 represents a switch between entry and clearance of Picornaviridae. Nature541(7637), 412.

Members

Thijn Brummelkamp
Group leader
Abdelghani Mazouzi
Post Doc
Danielle Bianchi
Phd Student
Felix van der Krift
Post Doc
Gian-Luca McLelland
Post Doc
Luka Wolf
Post Doc
Marleen Dekker
Phd Student
Nicolaas Boon
Technician
Rafaela Alves de Oliveira
Phd Student
Rob Kammen    
Technician