IL-10 as a therapeutic agent for preterm birth prevention

3-Year PhD Studentship in Reproductive Health Sciences

Supervisors - Supervisors Jane Norman (MRC CRH) [Email Address Removed] and Adriano Rossi (CIR)

Project - IL-10 as a therapeutic agent for preterm birth prevention

The Medical Research Council (MRC) Centre for Reproductive Health (MRC-CRH) conducts research into conditions that affect reproductive fitness and the health of male and female reproductive organs including infertility, endometriosis and premature birth. The Centre brings together scientists who have outstanding strengths in reproductive biology, stem cells, inflammation, development, hormonal disease and imaging. We provide a rich environment for training of clinical and non-clinical scientists and a vibrant programme of activities aimed at encouraging public engagement in science.

Three 3-year PhD Studentships will be available in September 2013 to outstanding science graduates wishing to pursue a career in Reproductive Health Sciences. The studentship will cover tuition fees at the UK/EU rate, a stipend (currently £13,726) with a rise each year to match inflation. This PhD Programme seeks to attract the best students from across the UK and EU to join our internationally recognised research community of Reproductive Health Scientists in Edinburgh. The Centre has a thriving postgraduate community of more than 30 MSc and PhD trainees who are mentored by a postgraduate studies committee.

Applicants are expected to have a good honours degree in the sciences (biological, chemical or physical), at least UK level of 2.1 or the equivalent from non-UK universities. A Master’s degree in relevant subject would be an advantage.

The Little France Campus

The Centre for Reproductive Health is located on the ground floor of the Queen’s Medical Research Institute on the University of Edinburgh’s Medical Campus at Little France. (http://www.ed.ac.uk/schools-departments/medicine-vet-medicine/about/little-france) The CRH enjoys close collaborative links with the other Centres on the Little France Campus including the MRC Centre for Inflammation Research (MRC-CIR); the British Heart Foundation Centre of Excellence in Cardiovascular Science (BHF-CVS) and the Clinical Research Imaging Centre (CRIC) and the MRC Centre for Regenerative Medicine (CRM).

Project Background
Good evidence suggests that preterm labour is an inflammatory event. Anti-inflammatory agents are likely therefore to be effective therapies(1). We have recently investigated the role of lipoxins (pro-resolution lipid mediators) in a mouse model of preterm labour, but these appear insufficiently effective when applied in vivo.
In this project, we will explore the role of IL-10 as a potential novel therapy. We will use both human tissue and a mouse in vivo model to explore effects and likely efficacy.

Evidence for a potential role for IL-10 comes from several lines of evidence. Firstly, IL-10 null mice have increased sensitivity to LPS induced fetal loss (due to prematurity), an effect which can be abrogated by exogenous IL-10. Preliminary studies in wild type mice suggest that exogenous IL-10 reduces the adverse impact of LPS on fetal viability, but has no effect on birthweight (2). Secondly, intravenous IL-10 reduced intra-amniotic IL-1 induced increase in myometrial contractility in pregnant rhesus monkeys in the last third of pregnancy (3). Thirdly, IL-10 is able to suppress LPS induced cyclo-oxgenase 2 expression in preterm (although not term) placental explants (4). Importantly, rat studies suggest that IL-10 may inhibit maternal infection induced pup brain white matter injury(5).
Much of the exploratory work so far has focused on the effects of IL-10 on the placenta. Here, we will focus on the myometrium, the major effector organ of parturition.

Aims
The aim of this study is to explore a potential therapeutic role for IL-10 in human parturition. Specifically we aim to:
1. Determine whether IL-10 reduces LPS induced myometrial contractions, using our PHM1 myometrial cell line as an in vitro contraction model.
2. Determine whether IL-10 can inhibit myometrial production of prostaglandins and cytokines.
3. Determine the mechanism of action of IL-10 preterm labour and brain injury prevention in a mouse model by studying molecular and anti-inflammatory mechanisms associated with IL-10 induced preterm labour prevention.

This project will give the student exposure to cell culture, ELISA, RT-PCR, histology, fluorescence activated cell sorting and animal models. The project will be supported by members of the Norman and Rossi labs, with day to day support available from Marian Aldhous and Graham Harold (post doc and technician in the Norman lab). Informal enquires are welcome, but all applications MUST be via [Email Address Removed]

Funding
This project is funded by Tommy’s the baby charity.

How to Apply

For application, please submit a copy of:
• A curriculum vitae
• A ‘statement of purpose’ outlining your reasons for undertaking this programme of study and how you see it affecting your career plan, together with an indication of which project you are interested in (see list below)
• 3 academic references should email/send letters on your behalf to: [Email Address Removed]

PLEASE NOTE Applications sent directly to project supervisors may not be counted.

The closing date to apply for these studentships is Monday 11 March 2013.

If you have any questions regarding the programme please contact the programme secretary [Email Address Removed]