CellCircuits: Mining a genomics compendium to identify therapeutic targets
Brummelkamp Laboratory, The Netherlands Cancer Institute (NKI), Amsterdam
Wessels Laboratory, The Netherlands Cancer Institute (NKI), Amsterdam.
Scenic Biotech BV, Amsterdam, The Netherlands
Project description. Human cells perform highly complex tasks and are equipped with the required machinery and decision-making processes that largely remain poorly understood. Although human genes play a central role, no wiring diagram exists depicting their function. This project will link the function of all human genes to a compendium of cellular processes. This will suggest new entry points to manipulate cellular processes and therapeutic strategies to rebalance disease.
Public-private, multi-disciplinary collaboration. This consortium will draw upon 1) Phenosaurus, a large collection (~130) of haploid screens generated in collaboration with Scenic Biotech BV employing the Cell-seq technnology developed by the Brummelkamp laboratory; 2) the screening, cell and molecular biology expertise of the Brummelkamp laboratory and the computational know-how of the Wessels laboratory. With the Cell-seq technology proven to be highly effective, the opportunity exists now to cover diverse cellular functions and to use advanced computational network inference approaches to deduce the underlying genetic control mechanisms.
The successful candidate will be employed in the Wessels and Brummelkamp groups at the Netherlands Cancer Institute, and will regularly liaise with Scenic Biotech to generate sufficient cohesion and momentum.
Candidate profile. We are seeking a highly motivated PhD candidate with:
- A degree in bioinformatics, computer science or a related discipline
- Experience in statistics, machine learning and/or pattern recognition
- Proficiency in bioinformatics programming languages (e.g. R, Python)
- Good cross-disciplinary collaborative and communication skills
- Experience in analysing high-throughput molecular data is a plus
- Experience in cancer biology and clinical applications is a plus
Interested? Please send CV and motivation letter to Lodewyk Wessels (firstname.lastname@example.org). Please include the names and contact information of at least two references.
Deadline: 1 October 2019
- Brockmann, M., Blomen, V.A., Nieuwenhuis, J., Stickel, E., Raaben, M., Bleijerveld, O.B., Altelaar, A.F.M., Jae, L.T. 1 and Brummelkamp, T.R1. (2017) Genetic wiring maps of single-cell protein states reveal an off-switch for GPCR signalling. Nature 546, 307-311.
- Nieuwenhuis, J., Adamopoulos, A., Bleijerveld, O.B., Mazouzi, A., Stickel, E., Celie, P., Altelaar, M., Knipscheer, P., Perrakis, A., Blomen, V.A., and Brummelkamp, T.R. (2017) Vasohibins encode tubulin detyrosinating activity. Science 6369, 1453-1456.
- Mezzadra, R. 1, Sun, C. 1, Jae, L.T. 1, Gomez-Eerland, R., de Vries, E., Wu, W., Logtenberg, M.E.W., Slagter, M., Rozeman, E.A., Hofland, I., Broek,s A., Horlings, H.M., Wessels, L.F.A., Blank, C.U., Xiao, Y., Heck A.J.R., Borst, J., Brummelkamp, T.R. and Schumacher, T.N.M. (2017) Identification of CMTM6 and CMTM4 as PD-L1 protein regulators. Nature 549, 106-110.
- Logtenberg MEW, Jansen JHM, Raaben M, Toebes M, Franke K, Brandsma AM, Matlung HL, Fauster A, Gomez-Eerland R, Bakker NAM, van der Schot S, Marijt KA, Verdoes M, Haanen JBAG, van den Berg JH, Neefjes J, van den Berg TK, Brummelkamp TR, Leusen JHW, Scheeren FA, Schumacher TN. (2019) Glutaminyl cyclase is an enzymatic modifier of the CD47- SIRPα axis and a target for cancer immunotherapy. Nature Medicine 4, 612-619.