Netherlands: PhD Position in Building minimal cells to understand active cell shape control at FOM Institute AMOLF

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Job description

The project is divided in three sub-projects that are each led by one team member, with close collaborations within the team and with the other members of the Biological Soft Matter group. Moreover, we will make a direct connection to biological functions by confronting our in vitro results with in vivo observations of active cell shape changes during fruit fly embryogenesis, in close collaboration with developmental biologists.

PhD student, sub-project 1:
Given the molecular complexity of the cortex-membrane interface, it has been difficult to clearly delineate the molecular mechanisms that contribute to cortex-membrane crosstalk. You will address this question by building minimal cell models composed of planar lipid bilayers coupled to an active actin-myosin cortex. You will integrate the bilayers with microfluidic flow devices, which will permit sequential in-flow of different cortical proteins. The 2D-geometry of supported bilayers will further enable us to use advanced microscopy techniques that permit single-molecule resolution, in particular total internal reflection microscopy (TIRF) and Photoactivated Localization Microscopy (PALM).

PhD student, sub-project 2:
Cell shape is critically dependent on the mechanical properties of the cell surface. The elastic properties of bare lipid bilayers are well understood, but we have only a rudimentary understanding of composite membranes consisting of a bilayer coupled to a cytoskeletal polymer network. Even less well understood is the influence of molecular motor activity on the elasticity and shape of membranes. To resolve the microscopic basis of cell shape control, you will build minimal cell models based on giant unilamellar vesicles (GUVs). You use microfluidics approaches to generate GUVs of a controlled size with an active actin cortex. By combining micromanipulation tools (optical tweezers and micropipettes) with confocal fluorescence microscopy, the shape of the GUVs can be directly related to their active and passive mechanical properties.

Research
You will work in a team of two PhD students and one postdoc, embedded within the Biological Soft Matter group, to resolve the biophysical mechanisms that enable cells to actively control and change their shape by cortex-membrane interactions.

This project funded by an ERC Starting Grant aims to understand the biophysical mechanisms that enable cells to achieve precise and reproducible changes in shape. Changes in cell shape are essential for vital cellular functions, such as growth, division, and movement, during embryonic development and throughout life. Conversely, dysregulation of cell shape can lead to life-threatening diseases such as cancer and developmental defects. The main determinants of cell shape in animals and humans are the cell membrane and a thin polymer gel beneath it that is known as the actin cortex. This cortex has the remarkable ability to drive shape changes by means of molecular motors that actively generate contractile forces. Cells tightly control their shape by balancing active forces with passive forces arising from cortex-membrane adhesion and elasticity. However, it remains an open question how these different forces are generated and controlled on the molecular level, due to the enormous molecular complexity of cells. We aim to combine model biomembranes and active actin networks into biologically relevant cell-free model systems that will allow us to resolve the physical basis of active cell shape control. We will focus on cortex-membrane interactions mediated by the linker protein septin, which plays a universal and essential role in cell shape control in all animals.

Requirements

We are looking for outstanding experimental physicists, physical chemists, or physical biologists with a strong interest in the interface of biophysics and biology. Since the project involves international collaborations, we seek a candidate with excellent communicative and organizational skills.
Candidates must meet the requirements for an MSc degree.

Conditions of employment

When fulfilling a PhD position at the FOM foundation, you will get the status of junior scientist.
You will have an employee status and can participate in all the employee benefits FOM offers. You will get a contract for four years. Your salary will be up to a maximum of 2.636 euro gross per month.The salary is supplemented with a holiday allowance of 8% and an end-of-year bonus of 8,33%.
You are supposed to have a thesis finished at the end of your four year term with FOM.
A training programme is part of the agreement. You and your supervisor will make up a plan for the additional education and supervising that you specifically need. This plan also defines which teaching activities you will be responsible (up to a maximum of 10% of your time). The conditions of employment of the FOM-foundation are laid down in the Collective Labour Agreement for Research Centres (Cao-Onderzoekinstellingen), more exclusive information is available at this website under Personeelsinformatie (in Dutch) or under Personnel (in English).
General information about working at FOM can be found in the English part of this website under Personnel. The ‘FOM job interview code’ applies to this position.

Contract type: Temporary, four years

Organisation

FOM Institute AMOLF

FOM Institute AMOLF performs leading fundamental research on physics of Biomolecular Systems and Nanophotonics; two areas with key potential for technological innovations. The Institute contributes to knowledge transfer to industry and society and trains talented young researchers. AMOLF is located at Science Park Amsterdam, The Netherlands, and engages approximately 140 scientists and 70 support staff. See alsowww.amolf.nl/www.amolf.nl

The Biological Soft Matter group is an experimental research group that focuses on the physical properties of living cells. Our central aim is to understand the physical mechanisms that govern the self-organization and (active) mechanical properties of the cell’s cytoskeleton. We have two main research lines:

1. Cytoskeletal model systems: we reconstitute minimal cells from purified cytoskeletal proteins within cell-sized microchambers or liposomes. This approach enables us to dissect the roles of polymer physics, motor protein activity, and active filament (de)polymerization.
2. Cellular mechanoresponse: we study living cells inside extracellular matrices that mimic the cells’ natural tissue environment. Our aim is to understand the mechanisms that underlie cellular mechanosensing and -response.

Key technologies in our lab are advanced microscopy and quantitative image analysis, optical tweezer manipulation, optical microrheology, and rheology. We strive to learn biological design principles that can be applied to new supramolecular materials with biomimetic properties, such as the incredible strength or active nature of living cells. At the same time, we contribute a physics component to the fields of mechanobiology and tissue engineering. www.amolf.nl/research/biological-soft-matter/

Additional information

For information contact
Prof.dr. Gijsje Koenderink 
Group leader Biological Soft Matter
+31 (0)20 754 71 00

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