Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn

PhD: Dr Marian Brennan - Drug Development

This project will aim to develop of a novel biotherapeutic for the treatment of cystinosis.

Project description

Cystinosis is a rare condition that leads kidney failure and damage to other organs. It affects approximately 1 in 100 000 individuals globally. Damage occurs in cells due to the accumulation of cystine which crystalizes in the lysosome. This causes damage to the kidneys and eyes as well as other organs such as the thyroid, muscles and pancreas. End stage kidney failure occurs in patients by the age of 10 if left untreated.

In normal cellular function, proteins are broken down in the lysosomes resulting in their constituent amino acids. Cystine, a disulphide linked dimer of cysteine, is transported back into the cytoplasm by the cystine transporter (CNTR) for re-use in the synthesis of proteins. Patients with cystinosis are not able to transport cystine out of the lysosome due to a mutation in the CNTR gene. This causes a build-up of cystine in the lysosomes which ultimately causes damage to the cell. Patients with cystinosis present first with kidney damage, however, they also have damage to other organs such as the lungs and eyes. The project involves the design, production and testing of a biotherapeutic for the treatment of cystinosis. Computer modelling will be used to design a biotherapeutic that can be absorbed in the stomach and delivered to the lysosome using established methods. Specific modifications will be made to the protein structure to ensure maximum absorption and delivery of the protein. The biotherapeutic will then be produced and tested in the laboratory for binding to cystine and to test for functionality in cell based assays. The project involves both computational modelling as well as laboratory experimental work. Training in computational molecular modelling, molecular biology and cellular assays will be provided.

 
  • Research theme: Drug development, cystinosis, pharmaceutical sciences, molecular biology, cell biology, inborn errors of metabolism
  • Department: Molecular and Cellular Therapeutics
  • Tenure: Three - four years

Specification

  • Candidates should have a first class honours undergraduate degree or expect to receive a first class honours degree in microbiology, biochemistry, pharmacology or another biological science. 
  • English language requirements for candidates who do not speak English as their first language: an overall IELTS score of 6.5 or above.
Candidates should display:
  • A good knowledge base, with evidence of interest in this research area.
  • A capacity for independent thinking.
  • A professional work ethic.
  • Good organisational skills
  • Innovation and creativity.
  • Excellent interpersonal, communication and presentation skills.
  • A capacity to work collaboratively as part of a team as well as independently, in a non-structured environment.
  • Attention to detail, thoroughness in work practices and an ability to work to deadlines.

 

Application process

Please complete your application for this position here.   

  • Application deadline: Wednesday, 25 July 2018.

Mentors Dr Marian Brennan