School of Medicine, Dentistry
& Biomedical Sciences
BBSRC CASE PhD Funded Studentship: Sept 2011
Title of Project:
Supervisors:
Closing Date:
Elucidating the molecular mechanisms by which the bone morphogenetic protein
Grem1 contributes to diabetic kidney disease, Centre for Vision and Vascular
Science, QUB
Dr Derek Brazil (d.brazil@qub.ac.uk)
Professor Alan Stitt (a.stitt@qub.ac.uk)
Friday 29th April 2011, 5pm
The Centre for Vision and Vascular Science seeks applicants for a four-year PhD studentship funded by
Diabetes UK with an annual stipend of £17,500 approx, and to commence in September/October. The deadline
for applications is 5pm on Friday 29th April 2011.
The project will investigate “Elucidating the molecular mechanisms by which the bone morphogenetic protein
Grem1 contributes to diabetic kidney disease” and will be supervised by Dr. Derek Brazil and Professor Alan
Stitt (see website for more details: www.qub.ac.uk/researchcentres/CentreforVisionandVascularScience/)
We invite talented and motivated students, or graduates to apply for our PhD programme. Applicants should
be recent graduates or final year undergraduates who have or expect to get a first or upper second-class
honours degree or equivalent, and have laboratory or research experience (either as part of or outside of a
university degree course). The successful applicant will commence their PhD in September 2011. This project
will be carried out in collaboration with scientists in AstraZeneca and the successful candidate will have the
opportunity to spend up to 6 months onsite at AstraZeneca to carry out a portion of the research project.
Abstract:
Gremlin1 (Grem1) is an antagonist of bone morphogenetic proteins that plays a key role during limb and
kidney development in mammals. Expression of Grem1 and its BMP targets is a tightly regulated process, and
alterations in the levels of Grem1 and/or BMPs causes developmental defects such as impaired limb and digit
formation, and absence of kidney development. Grem1 expression in adult mammalian kidney is low, but is
reactivated in diseases such as diabetic nephropathy, glomerulonephritis and chronic allograft nephropathy.
Our recent data has shown that mice lacking one copy of the Grem1 allele are protected from the sequelae of
early diabetic nephropathy (Roxburgh et al., 2009). In addition, Grem1 deletion also protects mice from renal
fibrosis in the unilateral ureteral obstruction (UUO) model of acute renal injury. Given its significant role in
kidney disease, and the potential to target Grem1 in fibrotic kidney disease, it is of vital importance to
elucidate the precise molecular mechanism of Grem1-induced renal cell damage in models of diabetic
nephropathy.
The PhD studentship will build on previous data from Dr. Brazil’s laboratory to identify the molecular
interactions of Grem1 and its BMP targets during diabetic kidney disease. The successful student will use
cutting edge molecular cell biology experimental approaches within carefully-planned, sequential experiments
using protein biochemistry, cell culture systems and pre-clinical models of human disease. Modulation of BMP
signalling in disease is an exciting and dynamic area of academic research globally with several international
conferences dedicating sessions to discuss their mechanisms of action in disease (e.g. ISN Geneva 2010). This
project therefore offers an excellent opportunity to train a PhD student in this cutting-edge area with input
from industry (AstraZeneca) that will hopefully generate new lead compounds for the treatment of renal
fibrosis.
Applicants should hold or expect to have gained a first or upper second class honours degree in a relevant
biological science. The project is available for three years and is open to candidates from the EU.
Candidates should apply through the Queen's on-line application portal at: http://dap.qub.ac.uk/portal and
also submit a CV including a synopsis of research experience to Nancy Bowman (n.bowman@qub.ac.uk) by
the closing date of Friday 29th April 2011 at 5pm.
Please contact the supervisor if you require additional information on this studentship.