2 PhD Candidates to study transcription factor binding at the single-molecule level

2 PhD Candidates to study transcription factor binding at the single-molecule levelLeiden University was founded in 1575 and is one of Europe's leading international research universities.The Faculty of Science, the Leiden Institute of Physics (LION) and the Netherlands Cancer Institute (NKI) are looking for:2 PhD Candidates to study transcription factor binding at the single-molecule levelPrecise regulation of transcription is essential to ensure that the correct genes are expressed in the correct tissue at the correct time. At the basis of gene regulation are gene-specific transcription factors (TFs), which are essential to activate or repress transcription of their target genes in specific tissues. Previous work from our and other labs (Pomp, Mol Cell, 2024) have shown that many TFs bind to DNA cooperatively, but how this cooperativity is established is largely unclear. In the first project (Tineke Lenstra group, NKI), we aim to uncover how transcription factor binding dynamics and cooperativity are regulated by nucleosomes, self-interactions, and DNA shape, and how these mechanisms regulate single-cell transcription dynamics. In the second project (John van Noort group, Leiden University), we will design and build custom chromatin fibers to resolve how these are folded into higher-order structures and how chromatin structure affects transcription factor binding. The projects are tightly linked, and it is anticipated that both PhD's work together closely.In collaboration with LUMICKS, manufacturer of C-trap instrumentation, we will set up a novel single-molecule imaging system to measure and perturb the DNA binding kinetics of transcription factors ex vivo and develop a novel assay to map the position of nucleosomes along single chromatin fibers. Moreover, we will exploit the unique opportunity to integrate these ex vivo results with simultaneous DNA binding and transcription measurements at a single locus in living yeast cells using our novel tracking technology (Pomp, Mol Cell, 2024). This powerful ex vivo-in vivo combination will allow us to gain quantitative insight into the different mechanisms of transcription factors cooperativity in gene regulation at single molecule resolution.Your profileWe are looking for ambitious and enthusiastic PhD candidates with a strong background in biophysics, molecular biology, biochemistry, or quantitative biology. Previous experience with single-molecule force spectroscopy and/or fluorescence, protein purifications, or in vitro eukaryotic transcription assays is advantageous. The candidates should be creative, independent, and have a problem-solving attitude. Good communication skills and the ability to work in a multi-disciplinary team are essential.Terms and conditionsWe offer a stimulating and interactive research environment, free use of all state-of-the-art facilities, and a competitive salary. Salary ranges from €2,770 to €3,539 gross per month (pay scale P in accordance with the Collective Labour Agreement for Universities). The appointment is for a period of at least four years. In addition, you will receive 8% holiday pay and end-of-year bonus (8%).How to applyAre you enthusiastic about this vacancy? We are looking forward to getting to know you. Please submit your application online through the blue button below. Please ensure that you upload the following additional documents:Applications are written in English and include aCover Letter indicating the motivation for the projectCopies of transcripts of degrees obtainedContact details of two references (ideally at least one of them with extensive EU experience)The inclusion of a two-page project proposal is highly encouraged and will be an evaluation benefitApplications should be submitted as a single PDF file.Interested candidates can respond until both vacancies are filled.

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