PhD: Role of the cytoskeleton in cell membrane electroporation and cargo translocation
New genome editing tools promise to repair cell functions at the source. However, they require the delivery of nucleic acids and/or gene editing enzymes …
- Mekelweg, Delft, Zuid-Holland
- Tijdelijk contract / Tijdelijke opdracht
- € 2443 - € 3122 per maand
New genome editing tools promise to repair cell functions at the source. However, they require the delivery of nucleic acids and/or gene editing enzymes directly into cells. Electroporation by transient disruption of the membrane under electric pulses can in principle deliver cargo molecules straight to the cytosol. However, the mechanisms that determine the efficiency of electroporation across the cell membrane are unknown. We recently discovered that the actin cytoskeleton, a crosslinked network of filamentous proteins that lines the cell membrane, plays an important role in the barrier function of the cell surface. The aim of this experimental PhD project is to reveal the biophysical mechanisms by which the actin cortex and the membrane together govern electro-transfer of nucleic acids and proteins across the cell membrane. To this end, you will harness techniques developed by the Koenderink lab to create synthetic cell-like lipid vesicles with tunable cytoskeleton-membrane interactions. To measure the mechanical behavior of the membrane-cytoskeleton interface, you will develop novel microfluidic aspiration devices. Finally, you will use high resolution microscopy combined with microfluidic electroporation devices to visualize the electro-transfer of model cargoes (DNA/proteins) and CRISPR-Cas gene editing molecules across the membrane of the synthetic cells. By teaming up with a PhD student in Pouyan Boukany’s lab who will study electroporation in living cells and with the team of Lea Rems for membrane simulations, we will be able to understand the mechanisms that govern electroporation efficiency as a prerequisite toward the future rational design of robust and safe methods for non-viral delivery of gene-editing molecules.
We offer an inspiring, supportive and collegial environment. The Koenderink lab is an experimental biophysics lab studying the mechanobiology of cells and tissues. We combine concepts and techniques from soft matter physics, biophysics, synthetic biology, protein engineering, and cell biology. The Koenderink lab is embedded in the TU Delft Department of Bionanoscience, which focuses on the fundamental understanding of biological processes from molecule to cell. The department features an inspiring, international environment with access to state-of-the art facilities for nanofabrication, a microscopy facility, molecular/cell biology, biochemistry, and high-performance computing for image processing.
We hire outstanding experimental scientists with a strong affinity for research at the interface of physics and biology. Research experience in fields such as biophysics, soft matter science, single-molecule techniques, optical microscopy, or nanoscience is welcomed. We are looking for a candidate with a high level of intellectual creativity and genuine interest in fundamental research, who is keen to work in an international and interdisciplinary team. Women are particularly encouraged to apply, as they typically make up a smaller fraction of the applicant pool. Applicants must
- hold a Master’s degree, or approach its completion, in physics, chemistry, (bio)engineering, materials science, nanoscience, or a closely related discipline;
- have excellent written and spoken English skills;
• thrive in an international, multidisciplinary and highly collaborative environment.
Doing a PhD at TU Delft requires English proficiency at a certain level to ensure that the candidate is able to communicate and interact well, participate in English-taught Doctoral Education courses, and write scientific articles and a final thesis. For more details please check the Graduate Schools Admission Requirements.
Doctoral candidates will be offered a 4-year period of employment in principle, but in the form of 2 employment contracts. An initial 1,5 year contract with an official go/no go progress assessment within 15 months. Followed by an additional contract for the remaining 2,5 years assuming everything goes well and performance requirements are met.
Salary and benefits are in accordance with the Collective Labour Agreement for Dutch Universities, increasing from € 2443 per month in the first year to € 3122 in the fourth year. As a PhD candidate you will be enrolled in the TU Delft Graduate School. The TU Delft Graduate School provides an inspiring research environment with an excellent team of supervisors, academic staff and a mentor. The Doctoral Education Programme is aimed at developing your transferable, discipline-related and research skills.
The TU Delft offers a customisable compensation package, discounts on health insurance and sport memberships, and a monthly work costs contribution. Flexible work schedules can be arranged. For international applicants we offer the Coming to Delft Service and Partner Career Advice to assist you with your relocation.