Finding drugs that ameliorate senescence to improve health outcomes in Alstrom syndrome

The project:

We seek a motivated basic science PhD candidate to join a multi-disciplinary research team of basic scientists and clinicians to find new therapies for the ultra-rare disease Alstrom syndrome. We work closely with the patient organisation Alstrom syndrome UK (https://www.alstrom.org.uk/). This project will give training in a wide range of experimental techniques, and provide ample opportunities to interact with the clinical service and the patient organisation, if desired.

You will be part of a cohort of 5 PhD students in the LifeArc ARDT Centre (see below).

The disease:

Alstrom syndrome (AS) is an ultra-rare disease with multi-organ involvement, including visual and hearing impairment, obesity, kidney disease and type2 diabetes. The reduced life expectancy (~ 55 years) is caused by heart failure and kidney or liver impairment. Excessive fibrosis of organs is often observed. The cause of AS is the recessive loss of ALMS1, encoding a primary cilia protein with largely unknown functions.

Aims: In this project you will a) set up multi-organ cellular models for AS, b) perform a therapeutic screen to test senescence modulating drugs and c) evaluate the most promising drugs in patient-derived cell models of kidney disease in AS.

Experimental approaches:

You will employ stem cell derived cell models for AS. We will train you in differentiating cells into cardiomyocytes, fibroblasts and pancreatic beta-cells. You will be supported to establish human Urine-derived Renal Epithelial Cells (hURECs) from AS patients. hURECs represent renal tubular epithelial cells. This part of the project is in collaboration with the University of Newcastle.

Outcomes:

This project will establish stem-cell- and patient-derived cellular models for pathology of various tissues in AS. It will confirm senescence as an overarching pathology. The drug screen will identify a viable avenue for translation to improve health outcomes in AS patients.

Information on LifeArc ARDT Centre

Globally, there are more than 300 million people living with rare diseases. However, clinical trials for rare diseases are challenging and can be a major limiting step in getting new treatments to patients. The research can be fragmented, and researchers sometimes lack access to specialist facilities, as well as advice on regulation, trial designs, preclinical regulatory requirements, and translational project management.

The LifeArc Centre for Acceleration of Rare Disease Trials brings together a consortium of three universities from across the UK: Newcastle University, Queen’s University Belfast, and University of Birmingham. They are pooling their expertise in a

£12M Centre to focus on improving the efficiency of rare disease trials and increasing the number of opportunities for patients to take part. Researchers will develop a UK ‘4 nations’ approach to deliver trials of new treatments using ‘one stop’, patient friendly models.

This will speed up the delivery of clinical trials for people with rare diseases and enable more rapid approval of new therapies for use in the NHS.

More information on the Centre can be found here: https://www.birmingham.ac.uk/research/centres-institutes/rare-disease-studies/lifearc-centre and here: https://www.lifearc.org/project/lifearc-translational-centres-for-rare-diseases/

As part of the Centre, LifeArc and the University of Birmingham are funding 5 non-clinical PhD studentships to work on translational projects involving different rare diseases. These PhD projects will provide essential evidence and models to allow treatments to be tested in rare disease clinical trials of the future.

If you plan to apply, please contact Prof. K Gehmlich (k.gehmlich@bham.ac.uk) for required documents.