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

1 PhD Candidate to study transcription factor binding to chromatin at the single-molecule level

Ensuring that the correct genes are expressed in the right tissue at the appropriate time is fundamental to gene regulation. At the core of this process are gene-specific transcription factors (TFs), which play a vital role in activating or repressing the transcription of their target genes in specific tissues. Previous research (Pomp, Mol Cell, 2024) has demonstrated that many TFs bind to DNA cooperatively. However, the mechanisms underlying this cooperativity remain largely unclear. The precise location of promoter sites within chromatin fibers is likely crucial for TF binding site accessibility, but the complexity of in vivo chromatin presents significant challenges to gaining mechanistic insights.

In this project, we aim to design and construct custom chromatin fibers composed of dozens of nucleosomes to elucidate how these structures fold into higher-order configurations and how chromatin architecture influences transcription factor binding. Concurrently, a second PhD candidate in the Tineke Lenstra group at the Dutch Cancer Institute will investigate how transcription factor binding dynamics and cooperativity are regulated by individual nucleosomes, self-interactions, and DNA shape, and how these mechanisms govern single-cell transcription dynamics. You will collaborate closely and receive support from a multi-disciplinary team from both labs.

In partnership with LUMICKS, the manufacturer of C-trap instrumentation, we will establish a novel single-molecule imaging system to measure and manipulate the DNA binding kinetics of transcription factors ex vivo. Additionally, we will develop a new assay to map the positions of nucleosomes along single chromatin fibers. Your role will involve designing unique chromatin fiber structures with specific functionalities, developing and testing new force-spectroscopy protocols—initially with Magnetic Tweezers and subsequently with optical tweezers—and physically modeling the resulting single-molecule force spectroscopy data. You will integrate single-molecule fluorescence and DNA unzipping with chromatin unfolding, incorporating sequence-dependent features into your design and analysis.

Your profile

• We are seeking an ambitious and enthusiastic PhD candidate with a strong background in biophysics. The ideal candidate will have:
• An MSc in physics, or a demonstrated strong interest in (bio-)physics, as evidenced by a significant component in your curriculum.
• Previous experience with single-molecule force spectroscopy and/or single-molecule fluorescence microscopy is highly advantageous.
• Creativity, independence, persistence, and a problem-solving attitude.
• Excellent communication skills and the ability to work effectively in a multi-disciplinary team.
• If you are passionate about advancing your career in biophysics and meet these qualifications, we would love to hear from you!
  

Our organization
The 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 address visit our website (physics.leidenuniv.nl/vannoort) or contact John van Noort, (noort@physics.leidenuniv.nl).

How to apply
Are you enthusiastic about this vacancy? We are looking forward to getting to know you. Please submit your application online using 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)
• Applications should be submitted as pdf files.

Interested candidates can respond until the vacancy is filled.

Acquisition in response to this vacancy is not appreciated.

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