Project properties

Title Microfluidic force spectroscopy of protein droplets on DNA
Group Biochemistry, Laboratory of
Project type thesis
Credits 12-36
Supervisor(s) Kasper Arfman
Examiner(s) Joris Sprakel, Hanne van der Kooij
Contact info Kasper.arfman@wur.nl
Begin date 2023/01/09
End date 2025/08/01
Description Transcription factors (TFs) are proteins that can boost or suppress the expression of genes by binding to DNA. How they achieve this remains a mystery: what happens to the DNA when TFs bind to it? It has recently been discovered that TFs can cluster on the DNA, producing droplets that behave as a fluid[1]. The biological purpose of these droplets remains a mystery, and much is still unknown about how these droplets form. We develop a single-molecule fluorescence technique to visualize how TFs bind to individual strands of DNA.

Current challenges in the development include: (i) controlling the attachment of DNA to a surface, (ii) extending the duration that we can image the DNA, and (iii) introducing target sequences or functional group to the biomolecules at study.
You will help us better understand how and why protein droplets form by tackling (one of) the abovementioned challenges.

References
1. Larson et al. (2017) Liquid droplet formation by HP1α suggests a role for phase separation in heterochromatin. Nature 547, 236–240.
Used skills
Requirements Interest in at least one of the following topics:
1. DNA/protein engineering.
2. Single-molecule fluorescence microscopy experiments
3. Attaching DNA to a glass surface via a method called ‘DNA curtains’.
The details of the project will be tailored to the students interest.