Imperial College London Featured PhD Programmes
Norwich Research Park Featured PhD Programmes
FindA University Ltd Featured PhD Programmes
Norwich Research Park Featured PhD Programmes
Max Planck Society Featured PhD Programmes

Using the fly kidney to develop new treatments for genetic kidney diseases


Project Description

Polycystic kidney disease is the most common hereditary cause of kidney failure in man. It comprises a spectrum of diseases of which Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common form in adults and Nephronophthisis (NPHP) the most common form in children. Apart from tolvaptan, a vasopressin receptor-2 antagonist in adult patients with ADPKD, there are no other therapies currently available. The majority of genes and proteins linked to PKD have been linked to structural or functional abnormalities in primary cilia (the cilia hypothesis) leading to these diseases being classified as ‘ciliopathies’. However, there is also a large body of evidence linking their functions beyond the cilia compartment

Since cystoproteins can form distinct protein complexes, it has been proposed that common (PC1, PC2) and rare (NPHP) cystoproteins are likely to function in a common cystic pathway. However, the precise cellular pathways through which they could function remains unclear. Recent studies of the Drosophila BICC1 homologue, BicC, discovered that its loss in flies leads to cyst-like structures in Malpighian tubules – the fly analogue of renal tubules. This is of interest since the Malpighian tubule is not ciliated and it is known that spontaneous mutations in Bicc1 lead to a PKD phenotype in mice. Thus, the fly kidney offers a unique opportunity to study an evolutionarily conserved mechanism which could underlie human PKD.

The major aims of this project are to utilize the adult fly kidney (Malpighian tubule) to identify the cellular basis for cyst formation in a simpler and non-ciliated system. The homologues of several cystoproteins have been linked to actin organization and endocytic trafficking though regulation of the GTPase Cdc42 in the nematode C.elegans. Therefore, we aim to test the hypothesis that defects in endocytosis and actin organization are responsible for cyst formation. Secondly, we aim to identify and characterize novel cystic genes, and dissect their genetic interactions with BicC and other known cystic genes. Finally, we will initiate chemical and genetic screens to identify potential compounds that could inhibit or retard cyst formation in BicC mutant flies. A clearer understanding of how BICC alters cellular organization and function, identification of how it interacts with other cystoproteins in flies as well as potential chemical or genetics modifiers, will clarify the molecular and cellular pathogenesis of PKD and reveal new targets for developing novel treatments.

Funding Notes

This project is open to self-funded students only.

Entry Requirements:
Candidates must have a first or upper second class honors degree or significant research experience.

References

Enquiries:
Interested candidates should in the first instance contact Prof Albert Ong, [email protected]

How to apply:
Please complete a University Postgraduate Research Application form available here: www.shef.ac.uk/postgraduate/research/apply

Please clearly state the prospective main supervisor in the respective box and select “Infection, Immunity and Cardiovascular Disease” as the department.

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 2005-2019
All rights reserved.