英国伦敦大学学院生物物理学研究助理职位

Research Associate

The appointment will be full time on UCL Grade 7. The salary range will be £33,353 – £40,313 per annum, inclusive of London Allowance.

Mechanics and morphogenesis of simple tissues:

This project seeks to understand what subcellular structures participate in the mechanics of cell monolayers, how these tissues sense and adapt to changes in their mechanical environment, and what mechanical forces underlie the individual cell behaviours leading to tissue morphogenesis and homeostasis.

Epithelial monolayers are amongst the simplest tissues in the body, yet they play fundamental roles in adult tissues, where they act as physical and mechanical barriers to separate the internal environment from the external environment, and in development, when the intrinsic forces they generate drive morphogenesis. At the molecular level, the mechanics of these simple tissues is believed to be dictated by the cytoskeletal and adhesive proteins that form the intercellular junctions that interface the constituent cells into a tissue-scale mechanical syncitium. Mutations in these proteins lead to diseases presenting symptoms of fragilised epithelia. However, a true quantitative understanding of how subcellular structures and individual cell behaviors govern tissue-scale monolayer mechanics is lacking. During development, tissue morphogenesis arises from the combination of a variety of individual cell behaviors such as oriented cell division, apical contraction, and cell intercalation. Similar cellular-scale behaviors also underlie the adaptation of tissues to changes in their mechanical environment. However, little is known about what mechanical forces and molecular processes act during each of these unitary cell behaviors. Mechanical forces appear to play a role in coordinating individual cell behaviors through mechanosensory feedback processes. At the molecular level, several candidate mechanosensors have been uncovered, yet our current understanding of mechanosensitivity remains largely qualitative.

The research will rely on a novel mechanical testing system recently developed in the Charras lab and interdisciplinary approaches to bridge the gap between molecular, cellular, and tissue-scales. The project will use live confocal microscopy, optogenetics, mechanical testing, and computational modelling. This work will be carried out in close collaboration with the laboratories of Dr Alexandre Kabla, Cambridge and Prof Buzz Baum, UCL. Work will be carried out at the London Centre for Nanotechnology ( www.london-nano.com ). This ERC-funded project builds on previous work by members of the team (Harris AR et al, PNAS, 2012; Kuipers DK et al, J Cell Sci, 2014; Harris AR et al, J Cell Sci, 2014; Wyatt TPJ et al, PNAS, 2015).

The Postholder will be responsible for carrying out experimental research on the project using techniques including, but not limited to, optogenetics, molecular cell biology, laser ablation, biophysical force measurement techniques (AFM, optical tweezers), and live confocal microscopy. The candidate will also be required to analyse the experimental data, write Matlab analysis programs, and design new experimental techniques.

This research position is funded for 3 years In the first instance.

The successful candidate will have a PhD in a relevant area of Life Sciences or Physical Sciences (or at least have submitted their thesis) with an outstanding track record of research and publications in high impact journals. Extensive experience in cell biology, biophysics and microscopy is essential. Additional experience in programming, developmental biology, molecular biology, and optogenetics will be an advantage.