Medical Research Council, Harwell Featured PhD Programmes
University of Kent Featured PhD Programmes
King’s College London Featured PhD Programmes
University of Kent Featured PhD Programmes
University of Manchester Featured PhD Programmes

Structure and function of specialised ribosomes in the Drosophila melanogaster brain and testis


Project Description

The average cell contains ~10 million ribosomes, comprised of ~80 ribosomal proteins and 4 rRNAs. Until recently it was thought that all ribosomes were the same. But substantial new evidence has revealed that ribosome heterogeneity provides an additional level of translational control. These different ribosome populations are termed ‘specialised ribosomes. How these specialised ribosomes translate specific mRNA pools remains a mystery. This project aims to understand how changes in ribosome composition alters ribosome structure and how this enables ribosomes to translate specific mRNA pools.

We have discovered differences in ribosome composition in Drosophila melanogaster brain and testis. mRNA translation is particularly important during sperm production and neural function so it will be exciting to understand how this novel mechanism of gene regulation is achieved and how it contributes to brain function and male fertility.

Using a cutting-edge combination of genetics, biochemistry, translatomics and structural biology this project will uncover the structure-function relationship of specialised ribosomes. To understand changes to ribosome structures this project will involve Cryo-EM and to determine which mRNAs specialised ribosomes translate we will use Ribo-Seq. This work has potential to shed light on the underlying mechanism of human diseases caused by mutations to ribosomal proteins e.g. Diamond-Blackfan.

Hypothesis
Specialised ribosomes regulate protein synthesis by targeting translation of specific pools of mRNAs through altered ribosome structure.

Objectives and approaches:
1-Determine protein composition of specialised ribosomes; TMT mass spec of in-vivo tagged ribosomal proteins.
2-Structural assessment of specialised ribosomes; Cryo-EM of purified ribosomes.
3-Determine translational output of specialised ribosomes; Ribo-Seq of purified ribosomes.
4-Understand biological importance of specialised ribosomes; CRISPR followed by fertility and behaviour assays of flies.

Novelty/Timeliness
The concept of specialised ribosomes has only recently emerged. Several
specialised ribosomes have been characterised but what is missing is the
mechanistic link between altered ribosomal structure and function. By combining
cutting-edge approaches, this proposal will tackle this from several diverse and
complementary viewpoints. This project combines structural analysis of
specialised ribosomes (purified and inside cells) with functional assessments
(translational output and fly phenotype) to provide mechanistic insight.

Further further information on Aspden Group:
http://aspdenlab.weebly.com

Further information on omics research at Leeds:
http://www.leedsomics.org


Funding Notes

White Rose BBSRC Doctoral Training Partnership in Mechanistic Biology
4 year fully-funded programme of integrated research and skills training, starting Oct 2019:
• Research Council Stipend
• UK/EU Tuition Fees
• Conference allowance
• Research Costs

Requirements:
At least a 2:1 honours degree or equivalent. We welcome students with backgrounds in biological, chemical or physical sciences, or mathematical backgrounds with an interest in biological questions.
EU candidates require 3 years of UK residency in order to receive full studentship

Not all projects advertised will be funded; the DTP will appoint a limited number of candidates via a competitive process.

View Website

How good is research at University of Leeds in Biological Sciences?

FTE Category A staff submitted: 60.90

Research output data provided by the Research Excellence Framework (REF)

Click here to see the results for all UK universities

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 2005-2018
All rights reserved.

Let us know you agree to cookies

We use cookies to give you the best online experience. By continuing, we'll assume that you're happy to receive all cookies on this website. To read our privacy policy click here

Ok