University of Sheffield Featured PhD Programmes
Ulster University Featured PhD Programmes
University of West London Featured PhD Programmes
Newcastle University Featured PhD Programmes
Loughborough University Featured PhD Programmes

Understanding Dynamic Intracellular Organization in Gene-Engineered Cells by Advanced Fluorescence Microscopy and Physical Micromanipulation

  • Full or part time
  • Application Deadline
    Tuesday, February 04, 2020
  • Funded PhD Project (Students Worldwide)
    Funded PhD Project (Students Worldwide)

Project Description

Background

The inside of living cells is highly organized. Nevertheless, cellular components constantly move around and all molecules constantly turn over. How can intracellular order exist in such turmoil? This is a fundamental question in cell biology and biophysics. What are the design principles underlying the internal organization of human cells? Here we focus on the microtubule cytoskeleton which is particularly important during cell division when the mitotic spindle forms to segregate the genetic material. The spindle is a fascinating structure: it builds itself and is extremely dynamic. In metaphase, microtubules are re-polymerized every minute and are constantly moved around by molecular motors. Nevertheless, the spindle always displays the same shape - it is a paradigm for a self-organized biological steady-state structure. Biochemical and mechanical events inside the spindle are perfectly coordinated. How is this coordination achieved?

Project

We will investigate how the spindle maintains its shape despite the constant flow of material from its center to the poles. We will focus on understanding the coupling between biochemistry and mechanics (forces). We will engineer cultured human cells by gene editing so that we can precisely image spindle dynamics and suddenly manipulate intracellular protein concentrations. Using mechanical manipulation (laser cutting), we will break parts of the spindle, changing force transmission as we manipulate the biochemistry. By observing what goes wrong when biochemistry and mechanics become uncoordinated, we will understand the mechanism of their coordination under normal conditions. Quantitative analysis of advanced fluorescence microscopy movies will provide a rigorous understanding of spindle biomechanics and aid biochemical in vitro reconstitutions, theoretical modelling and computer simulations of spindle self-assembly and dynamics.

Environment

The Surrey lab recently relocated to the Centre for Genomic Regulation (CRG) in Barcelona, Spain. The overall goal of the lab is to understand how the cytoskeleton self-organizes and reorganizes itself, for example to form the mitotic spindle during cell division. The Surrey team has pioneered novel microscopy-based approaches to advance our understanding of the molecular mechanisms underlying microtubule cytoskeleton function. The team is interdisciplinary consisting of biochemists, physicists and cell biologists. Advanced optical microscopy is a key method used in the lab.

The PhD researcher will integrate at the CRG in Barcelona in a research center with international teams representing a broad range of disciplines, with first class core facilities to support the research project, a wide range of seminars given by high-profile invited speakers, and courses on complementary and transferable skills. He/she will be part of the PhD community at the CRG, which is highly active in organizing scientific and social activities.

Information on the Surrey lab: https://www.crg.eu/en/programmes-groups/surrey-lab

Information on the CRG PhD Programme: https://www.crg.eu/en/content/training-phd-students/crg-international-phd-programme

Funding Notes

The studentship is funded for 3 years by 'la Caixa' Foundation.

Applications must be submitted online to the INPhINIT call from 'la Caixa' Foundation (View Website). Through this finder View Website you will find a description of the project offered by the Surrey Lab, by selecting CRG at the RESEARCH CENTRE drop-down list.

IMPORTANT: Candidates for this position must undertake trans-national mobility, which means that candidates must not have resided or carried out their main activity (work, studies, etc.) in Spain for more than 12 months in the 3 years immediately prior to the call.

Application Deadline: 4 February 2020

References

Roostalu J, Rickman J, Thomas C, Nédélec F, Surrey T. Determinants of Polar versus Nematic Organization in Networks of Dynamic Microtubules and Mitotic Motors. Cell 175, 796-808 (2018).

Dogterom M, Surrey T. Microtubule organization in vitro. Curr Opin Cell Biol 25, 23-9 (2013).

Email Now

Insert previous message below for editing? 
You haven’t included a message. Providing a specific message means universities will take your enquiry more seriously and helps them provide the information you need.
Why not add a message here
* required field
Send a copy to me for my own records.

Your enquiry has been emailed successfully





FindAPhD. Copyright 2005-2020
All rights reserved.