Primary ‘cilia’ are sensory organelles that detect mechanical and chemical stimuli. They are found in most cells of the body including in kidney cells. Normal functioning primary cilia are required for the maintenance of cell polarity, which regulates tubular diameter and cell proliferation. While disruption of cilia leads to a number of diseases, known as ‘ciliopathies’, including diabetes, obesity and polycystic kidney disease. Amongst cystic kidney diseases, Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common genetic cause of renal failure and is associated with ciliary dysfunction. Kidney injury stimulates excessive cell proliferation, thus in turn promoting cyst formation (enlarged tubular diameter).
Via this project the PhD student will carry out multi-disciplinary translational research using both in vitro and in vivo approaches to study how ciliary defects accelerate cell proliferation and cause abnormal cell signalling in ADPKD. While the generic cause of ADPKD is well known (i.e. mutations predominantly in Pkd1 or Pkd2 genes), the precise role of cilia and the signalling pathways contributing to disease progression are less clear. ADPKD is a multi-organ disease affecting kidneys, liver, pancreas and the vasculature, that affects over 12 million people worldwide.
The aim of the project is to identify and functionally characterise new players in ADPKD with the ultimate aim of finding new ways to cure or slow down disease progression. The student will be exposed to a wide range of cutting-edge techniques including high resolution microscopy (fluorescent, light, transmitting), next-generation RNA sequencing (RNA-seq, single cell RNA-seq, CHIP-seq and CLIP-seq), mass spectrometry, flow cytometry and in vivo models of disease (e.g. Pkd1 global and tissue specific knockouts). In addition, the student will have access to a wide range of seminars and additional training opportunities through the Sheffield Medical School.
The Sheffield Medical School has a successful mentoring scheme for postgraduate students (including PhD), which provides personal and professional development, in addition to a number of career and personal development courses. We are proud holders of an Athena Swan Silver Award in recognition of our efforts to build a happy and rewarding environment for both female and male staff and students.
This work will be carried out the in the laboratory of Dr Maria Fragiadaki and Professor Albert Ong, for more information please visit our websites (https://www.sheffield.ac.uk/medicine/people/iicd/maria-fragiadaki