Robust synthetic cell abscission based on a thorough understanding of the required membrane remodeling process

Living cells are highly complex systems made of countless lifeless molecular components. We do not understand how these interact to form a living cell that sustains itself, grows and divides. The BaSyC initiative is a collaborative 10-year research program that aims to understand ‘how life works’ by building an autonomous self-reproducing synthetic cell from the bottom up. As a container, we use giant unilamellar vesicles, which are cell-sized, lipid bilayer-enclosed reaction compartments that can be visualized by real-time microscopy and directly manipulated using biophysical tools. The Koenderink and Dekker labs study the process of cell division, which requires constriction of the cell into a dumbbell-shape, followed by neck abscission to split the cell into two daughter cells. Since the mechanism of abscission is still poorly understood, it remains a big challenge in the synthetic cell field to achieve robust cell division.

This experimental biophysics project aims to achieve robust synthetic cell abscission based on a thorough understanding of the required membrane remodeling process. You will reconstitute a minimal protein-based machinery for abscission, based on proteins such as the bacterial dynamin A and the ESCRT-like bacterial PspA. We anticipate that robust abscission requires these protein machineries to work in conjunction with lipid-based mechanisms that generate high spontaneous curvature at the neck. Asymmetries in head group size between the outer and inner leaflets triggered enzymatically or by photoactive lipids can for instance introduce high local curvature. Using quantitative confocal microscopy you will study how membrane binding and the abscission activity of the dynamins depend on lipid composition, whether dynamins have any intrinsic ability to generate curvature themselves, and what is the optimal neck diameter to achieve abscission. To create narrow necks, you will use optical-tweezers available in the Koenderink lab and DNA-nanotechnology tools from the Dekker lab. You will closely collaborate with other groups within the BaSyC consortium to ensure that the abscission pathway is compatible with other functionalities of the synthetic cell. The project will furthermore be carried out in close interaction with the groups of Siewert-Jan Marrink (Groningen) and Timon Idema (Delft), who will investigate abscission with simulations and analytical calculations.

You will be co-supervised by Gijsje Koenderink and Cees Dekker and will be embedded in both teams, which are conveniently located in the same department. The Gijsje Koenderink lab is an experimental biophysics lab that studies mechanisms of cell morphogenesis by bottom-up synthetic biology. The Cees Dekker lab is an experimental biophysics lab that explores a range of subjects from nanopore sequencing to chromosome biology, including microfluidics research. Both labs are embedded in the TU Delft Bionanoscience Department, which focuses on the fundamental understanding of biological processes from molecule to cell. The department features an inspiring and supportive international environment with access to state-of-the art facilities for microfluidics and nanofabrication (Kavli Nanolab), advanced imaging, molecular/cell biology, biochemistry, and high-performance computing for image processing.

Requirements

We seek an outstanding experimental biophysicist with a strong affinity for research at the interface of physics and biology and with relevant research experience in fields such as membrane, molecular, or cell biophysics or soft matter physics. We are looking for a candidate with a high level of intellectual creativity, genuine interest in fundamental research, who enjoys collaborations and easily communicates with scientists from different disciplines.

Applicants must

• hold a Master’s degree, or approach its completion, in physics, chemistry, or a closely related discipline;
• have excellent written and spoken English skills; 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.

– thrive in an international, ambitious, 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.

Conditions of employment

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 € 2541 per month in the first year to € 3247 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.

TU Delft (Delft University of Technology)

Delft University of Technology is built on strong foundations. As creators of the world-famous Dutch waterworks and pioneers in biotech, TU Delft is a top international university combining science, engineering and design. It delivers world class results in education, research and innovation to address challenges in the areas of energy, climate, mobility, health and digital society. For generations, our engineers have proven to be entrepreneurial problem-solvers, both in business and in a social context.

At TU Delft we embrace diversity as one of our core values and we actively engage to be a university where you feel at home and can flourish. We value different perspectives and qualities. We believe this makes our work more innovative, the TU Delft community more vibrant and the world more just. Together, we imagine, invent and create solutions using technology to have a positive impact on a global scale. That is why we invite you to apply. Your application will receive fair consideration.

Challenge. Change. Impact!