Pattern Formation in Growing Tissues - Biosciences, PhD (BBSRC Funded)

University of Exeter - College of Life and Environmental Sciences

The South West Biosciences Doctoral Training Partnership (SWBio DTP) is a BBSRC-funded PhD training programme in the biosciences, delivered by a consortium comprising the Universities of Bristol (lead), Bath, Cardiff, Exeter, and Rothamsted Research. Together, these institutions present a distinctive cadre of bioscience research staff and students with established international, national and regional networks and widely recognised research excellence. The partnership has a strong track record in advancing knowledge through high quality research and teaching in partnership with industry and government.

This project is one of a number that are in competition for funding from the South West Biosciences Doctoral Training Partnership (SWBio DTP). Up to 4 fully-funded studentships are being offered to start in September 2018 at the University of Exeter.

Academic Supervisors:

Main supervisor: Prof Steffen Scholpp
Co-supervisor: Prof Ashwin
Co-supervisor: Dr Kyle Wedgewood
Collaborator: Prof Trevor Dale
Collaborator: Dr Chrissy Hammond

Project description:

The process of subdividing a tissue into functional units represents a classic problem in pattern formation. Signalling proteins – so-called morphogens – orchestrate this process. The traditional view is that morphogens are released from local source and slowly diffuse through a neighbouring tissue to build up a gradient. As Wnt signals act as a key morphogen in tissue patterning, it is believed that similarly these signal proteins diffuse longrange to exert their morphogenetic function.

However, we have recently identified long signalling filopodia – socalled cytonemes – that tightly control transport of Wnt proteins. We have observed fast and directed distribution through expanding tissues. It is unclear how such a dissemination generates a stable and robust signalling gradient. The project includes:

  1. deciphering of the molecular mechanism of Wnt transport,
  2. simulating of the impact on patterning,
  3. validating the prediction in growing tissue.

Under the supervision of cell biologists and mathematicians, the student will experimentally alter cytoneme-based Wnt transport. The student will interfere with the length, frequency and direction of Wnt cytonemes by using chemical inhibitors, CRISPR/Cas9-based mutations and lentivirus-based infection methods in zebrafish and in human tissue. The student will use imaging-based, quantitative measurements of cytoneme-based Wnt transport from the source cells and a simultaneous description of the signalling gradient receiving tissue by using realtime PCR, single molecule fluorescence in-situ hybridisation, and advanced microscopy. Under the guidance of simulation experts, the student will test the findings and validate predictions in a stochastic, dynamic model.

The student selected for this project will develop invaluable skill sets in experimental genetics, 3D tissue culture, microscopy and mathematical modelling, whilst also making a significant contribution to the understanding of a biological pattern forming system. This combined skill set will make the candidate a highly desirable recruitment prospect for future academic and industrial employers. The Living Systems Institute (LSI), with complementary expertise in biosciences, mathematics and computer science will be an optimal environment to conduct these doctoral training studies. The LSI offers unique training opportunities for the PhD student as it allows the student address key problems in life sciences with state-of the- art equipment in an interdisciplinary environment. The centre facilitates interaction between empirical and theoretical scientists leading to the development of predictive modelling capacity from experimental data, leading to accurate, mechanistic descriptions of biophysical processes for entire ‘living systems’. The project includes close collaboration with the universities of Bristol and Cardiff to complement the required skill sets.

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South West England