- Are you inspired by the potential to use non-viral delivery of CRISPR-Cas complexes to reprogram mammalian cells for gene therapy?
- Are you fascinated by using novel microfluidics to deliver a precise number of genetic cargoes into primary human cells with minimal side effects?
- Are you eager to work in a high-end collaborative and interdisciplinary research environment related to gene delivery, biophysics, and microfluidics?
New genome editing tools (based on CRISPR-Cas complexes) promise to repair cell functions at the source by fixing disease-causing mutations. However, they require the delivery of nucleic acids and/or gene editing enzymes directly into cells so they can reach the cell nucleus via safe and effective approaches. Electroporation has become a popular and safe non-viral delivery method by transient disruption of the membrane under electric pulses. This technology can in principle deliver genetic cargoes straight to the cytosol under ideal pulses conditions. However, electroporation can also induce substantial cell death from extensive permeabilization of a cell membrane or generate poor transfection efficiency when electroporation is not optimized. Often, electroporation protocols have been optimized based on trial and error approaches, due to a lack of understanding on the underlying mechanisms of membrane proration and cargo translocations at the sub-cellular level. We recently elucidated that the actin cytoskeleton, a crosslinked network of filamentous proteins that lines the cell membrane, plays an important, hitherto unrecognized, role in the barrier function of the cell surface. The aim of this experimental Ph.D. project is to unravel the biophysical mechanisms by which the actin cortex and the membrane together govern electro-transfer of genes and proteins into living human cells. In this project, you will have the opportunity to work in a cutting-edge, fast-paced research environment, interact with researchers from many different disciplines, learn about fundamental biophysical and biological processes in living human cells, and interact with world-class collaborators. This highly interdisciplinary project is a collaboration between the Boukany lab at the Chemical Engineering Department, and the Koenderink lab at the Bionanoscience department at TU Delft and Leiden University Medical center (LUMC).
The research environment: We offer an inspiring, supportive and collegial environment. Delft University of Technology is a top-ranked research university, located in the Netherlands. The faculty of Applied Sciences has advanced clean-room and microscope facilities, offering very accessible and complete fabrication and analysis equipment. Its Department of Chemical Engineering (ChemE) is one of the leading schools in Europe. Within the Chemical Engineering Department, the Boukany research group focuses on fundamental and applied topics at the interface of engineering, soft matter, and biology, with a major emphasis on controlling and understanding the dynamics of biological systems. We will employ both experimental and theoretical approaches in our research to understand fundamental physics in soft-living systems. You will closely collaborate with several PhD/PD researchers (funded by the ERC-CoG, ZonMW and NWO-ENW) in the Boukany group work on the development of novel (bio)microfluidics and organon-a-chip devices for health-care applications (from diagnostics to therapeutics).
Qualifications: We hire outstanding experimental scientists with a strong affinity for research at the interface of physics, engineering and biology. Research experience in fields such as biophysics, soft matter science, single-molecule techniques, gene delivery, 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.
Conditions of employment: Ph.D. students are on a fixed-term (4 yr) contract. TU Delft offers a customisable compensation package, a discount for health insurance and sport memberships, and a monthly work costs contribution. Flexible work schedules can be arranged. Coming to Delft Service organizes diverse events for new international employees and their accompanying partners, like Partner Career Workshops and Dutch Culture Workshops. Located on campus are the International Children’s Centre and an international primary school which are subject to availability as well as several bilingual schools in the nearby surrounding. Salary and benefits are in accordance with the Collective Labour Agreement for Dutch Universities. As a PhD candidate you will be enrolled in the TU Delft Graduate School. TU Delft Graduate School provides an inspiring research environment; an excellent team of supervisors, academic staff and a mentor; and a Doctoral Education Programme aimed at developing your transferable, discipline-related and research skills.
Further reading in the attachment.