BBSRC SWBio DTP PhD studentship: Generation of the Wnt morphogenetic field in an growing tissue

This project is one of a number that are in competition for funding from the South West Biosciences Doctoral Training Partnership (SWBio DTP). The SWBio DTP is a BBSRC-funded PhD training programme in the biosciences, delivered by a consortium comprising the Universities of Bristol (lead), Bath, Cardiff and Exeter and Rothamsted Research. The SWBio DTP projects are designed to provide outstanding interdisciplinary training in a range of topics in Agriculture & Food Security and world-class Bioscience, underpinned by training in mathematics and complexity science. Each project will be supervised by an interdisciplinary team of academic staff and will follow a structured training 4-year PhD model.

Up to 4 fully-funded studentships at the University of Exeter are being offered to start in September 2017. The studentships will provide funding for a stipend (currently £14,296 per annum for 2016-17), research costs and UK/EU tuition fees at Research Council UK rates for 48 months (4 years) for full-time students, pro-rata for part-time students.

Academic Supervisors:

Main Supervisor: Prof Steffen Scholpp, University of Exeter
Co-supervisor: Prof Peter Ashwin, University of Exeter
Co-supervisor: Prof Christian Soeller, University of Exeter
Co-supervisor: Dr Chrissy Hammond, University of Bristol
Co-supervisor: Prof Robert Kelsh, University of Bath

Project Description:

The process of subdividing the vertebrate neural primordium into functional units i.e. forebrain, midbrain and hindbrain, represents a classic problem in pattern formation. Traditionally pattern modelling has been conducted at the continuum level with Turing instability models for pattern formation, which assume diffusion as mechanism for morphogen transport. So it was believed that Wnt signal proteins diffuses from a localised source, i.e. the posterior mesoderm, into the neural plate to build up a morphogenetic gradient. However, we have recently identified long signalling filopodia, which tightly control transport of Wnt proteins into the neural plate leading to the generation of a concentration gradient. It is unclear how a filopodia-mediated transport mechanism is able to generate a stable and robust morphogenetic gradient.

Under the supervision of developmental biologists, biophysicists and mathematician the student will alter experimentally filopodia-based signal Wnt transport during zebrafish neural plate patterning. Therefore, the student will interfere with the length, frequency and direction of Wnt cytonemes by using chemical inhibitors and CRISPR/Cas9-based mutations of filopodia effectors. The student will use a imaging-based, quantitative measurements of filopodia-based Wnt transport from the source cells and a simultaneous description of the receiving tissue i.e. dynamic cell migration and gene expression (e.g. using advanced microscopy and qRT-PCR) at different patterning stages.

Under the guidance of simulation experts, the student will construct a stochastic model to predict pattern formation. Different hypotheses for gradient formation will be plugged into the model and tested against observed patterns from experimental studies of wild-type, inhibitor-treated and mutant fish.


For further details and application please visit http://www.exeter.ac.uk/studying/funding/award/?id=2336