PhD Position Biophysical Origins of RNA Toxicity in Huntington’s Disease

Job description

In Huntington’s Disease (HD), expansion of CAG repeats in the huntingtin (HTT) gene leads to a toxic gain-of-function that ultimately results in fatal neurodegeneration. HD research has long focused on the toxic effects of the HTT-encoded polyglutamine protein that aggregates in neurons. However, recent discoveries reveal that the HTT mRNA itself forms condensates and aggregates, contributing to neuronal toxicity. In this project, your work will help define the origins of RNA toxicity in HD - a critical step toward developing therapies.

As a PhD candidate in this project, you will design, execute, and analyze single-molecule experiments using optical tweezers and confocal fluorescence imaging, building on previous work (O’Brien et al., Nat Comm 2024). Together with our collaborators, you will produce materials for these experiments and develop novel approaches for protein and RNA labeling. Working at the interface of biophysics and biochemistry, you will establish new paradigms that explain why some repeat RNAs are toxic while others are not.

• Independently conducting experimental work and performing data analysis
• Presenting your progress in regular team meetings
• Publishing your findings in peer-reviewed journals
• Participating in scientific conferences
• Supporting teaching and mentoring undergraduate and master's students

Under the mentorship of Prof. Christian Kaiser, you will have the freedom to explore your own ideas within the project goals. You will work closely with junior investigators in the group as well as with our local and international collaborators, and engage with the broader research community at the Bijvoet Centre and the Faculty of Science. Visit the Kaiser Lab and the Bijvoet Centre websites for more information.

• An MSc degree in (bio) physics, (bio) chemistry, or a related field
• Experience with wet lab work and data analysis
• Strong scientific writing and communication skills
• Proficiency in written and spoken English
• Experience with single-molecule approaches (not required, but a plus)

• a position for 18 months, with an extension to a total of four years upon successful assessment in the first 18 months
• a full-time working week and a gross monthly salary between €3.204 and €4.051 (salary scale P under the Collective Labour Agreement for Dutch Universities (CAO NU)). The salary is based on a 38-hour working week
• 8% holiday pay and 8.3% year-end bonus
• a pension scheme, partially paid parental leave and flexible terms of employment based on the CAO NU
• in addition to the terms of employment set out in our collective labour agreement, we offer attractive additional benefits, including opportunities for personal and professional growth, flexible leave arrangements, and extra vacation days

Read more about our terms of employment.

Universiteit Utrecht

A better future for everyone. This ambition motivates our scientists in executing their leading research and inspiring teaching. At Utrecht University, the various disciplines collaborate intensively towards major strategic themes. Our focus is on Dynamics of Youth, Institutions for Open Societies, Life Sciences and Pathways to Sustainability. Sharing science, shaping tomorrow.

Working at the Faculty of Science means bringing together inspiring people across disciplines and with a variety of perspectives and backgrounds. The Faculty has six departments:
Biology, Pharmaceutical Sciences, Information & Computing Sciences, Physics, Chemistry and Mathematics. Together, we work on excellent research and inspiring education. We do so, driven by curiosity and supported by outstanding infrastructure. Visit us on Linked In and discover how you can become part of our community.

You will work in an interdisciplinary research team led by Prof. Christian Kaiser. The lab is situated within the Molecular Biophysics and Biochemistry group, which employs diverse approaches ranging from cell biology methods to (bio) chemical and biophysical techniques, with systems ranging from self-assembled model structures to yeast and from bacterial and mammalian cells to the worm

C. elegans. The group is part of the Bijvoet Centre for Biomolecular Research (Department of Chemistry), which offers world-class expertise and infrastructure for various life science areas, including protein biochemistry and biophysics, mass spectrometry, and structural biology.