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

The Faculty of Science, the Leiden Institute of Physics (LION) and the Netherlands Cancer Institute (NKI) and are looking for:

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

Precise 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 setup 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 profile
We 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 skill and the ability to work in a multi-disciplinary team are essential.

Our organization
The second project will be hosted in the Leiden Institute of Physics (LION). LION is one of the oldest physics institutes in the Netherlands with more than 180 staff and around 30 senior scientists. LION is part of the Faculty of Science and covers a very broad spectrum of physics research and education. Theory and experiments go hand in hand at LION: from cosmology to mechanics of DNA, from granular matter to quantum nanoscience. LION has an active PhD community that organizes seminars and social events specifically for PhD students.

The Faculty of Science is a world-class faculty where staff and students work together in a dynamic international environment. It is a faculty where personal and academic development are top priorities. Our people are committed to expand fundamental knowledge by curiosity and to look beyond the borders of their own discipline; their aim is to benefit science, and to contribute to addressing the major societal challenges of the future.
The research carried out at the Faculty of Science is very diverse, ranging from mathematics, information science, astronomy, physics, chemistry and bio-pharmaceutical sciences to biology and environmental sciences. The research activities are organised in eight institutes. These institutes offer eight bachelor’s and twelve master’s programmes. The faculty has grown strongly in recent years and now has more than 2,300 staff and almost 5,000 students. We are located at the heart of Leiden’s Bio Science Park, one of Europe’s biggest science parks, where university and business life come together.

Terms and conditions
We offer a stimulating and interactive research environment, free use of all state-of-the-art facilities, 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%). The appointment is for a period of at least four years.

Diversity and inclusion
Diversity and inclusion are core values of Leiden University. Leiden University is committed to becoming an inclusive community which enables all students and staff to feel valued and respected and to develop their full potential.

Information
For further information and addresses visit our websites (https://www.nki.nl/research/research-groups/tineke-lenstra/, www.lenstralab.nl, and https://physics.leidenuniv.nl/vannoort) or contact John van Noort, (noort@physics.leidenuniv.nl) or Tineke Lenstra (t.lenstra@nki.nl).

How to apply
Are you enthusiastic about this vacancy? We are looking forward to get 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 a

• Cover Letter indicating the motivation for the project
• Curriculum vitae
• Copies of transcripts of degrees obtained
• Contact 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 benefit

Applications should be submitted as a single pdf file.
Interested candidates can respond until both vacancies are filled.

Acquisition in response to this vacancy is not appreciated.