Building a model of the HypothalamicPituitary-Gonadal (HPG) axis, BBSRC SWBio, PhD in Mathematics studentship (Funded) Ref: 3285 About the award Supervisors Lead Supervisor Professor Krasimira Tsaneva-Atanasov<http://emps.exeter.ac.uk/mathematics/staff/kt298>a, Department of Mathematics, College of Engineering, Mathematics and Physical Sciences, University of Exeter Additional Supervisors Professor Craig McArdle<http://www.bristol.ac.uk/clinical-sciences/people/craig-a-mcardle/index.html>, University of Bristol Dr Margaritis Voliotis<http://emps.exeter.ac.uk/mathematics/staff/mv286>, University of Exeter Location: University of Exeter, Streatham Campus, Exeter EX4 4QJ The SWBio DTP<http://www.bris.ac.uk/swbio/> is one of the 12 Doctoral Training Partnerships funded by the BBSRC to provide PhD training in areas of their strategic relevance. The SWBio DTP is a consortium comprising the Universities of Bristol (lead), Bath, Cardiff, Exeter, and Rothamsted Research. Together, these institutions present a distinctive cadre of bioscience research staff and students with established international, national and regional networks and widely recognised research excellence. The award: There are over 30 (including up to 5 CASE studentships) fully-funded 4 year studentships* available to start in September 2019 across a wide range of biosicence academic disciplines. This project is one of a number that are in competition for funding from the South West Biosciences Doctoral Training Partnership (SWBio DTP)<http://www.bristol.ac.uk/swbio/>. Up to 6 fully-funded studentships are being offered to start in September 2019 at the University of Exeter. Project Description: Gonadotropin-releasing hormone (GnRH) is secreted from hypothalamic neurones to control secretion of the gonadotropin hormones LH and FSH form the anterior pituitary, and thereby mediates central control of reproduction. It secretes in pulses and its effects are dependent on pulse characteristics (particularly pulse frequency). One of the most important recent discoveries in the field of reproduction is that of the KNDy system. This is a peptidergic neuronal oscillator that drives pulsatile GnRH secretion. It also mediates feedback effects of gonadal steroid hormones that are essential for key reproductive processes such as the timing of puberty and seasonal breeding (i.e. in farm animals) and the fine-tuning of gonadotropin secretion across the ovarian cycle. All of these components (hypothalamic pulse generator/pituitary pulse decoder/gonads) are absolutely essential for human reproduction so it is perhaps not surprising that all three are sites for therapeutic intervention, just as perturbation of any of them can cause infertility in disease states. We are convinced that mathematical and statistical approaches are required to fully understand such a complex system. To this end we have already generated a sophisticated mathematical model of the neuronal oscillator that we have trained on wetlab. data and are now using to explore possible mechanisms for modulation by gonadal steroids. Similarly, we have developed a mathematical model for the decoding of pulse dynamics by pituitary gonadotropes and have used this to explore cell-cell variability in responses to GnRH and its impact on information transfer. We now plan to take a similar approach to modelling effects of gonadotropin hormones on gonadal function, where we will have to introduce population dynamics as an additional feature (i.e. growth of granulosa cells before ovulation and formation of luteal cells thereafter). We then plan to simplify these sub-system models so that the components can be assembled into a meaningful model of the entire hypothalamo-pituitary-gonadal system. In this project the student will learn: • Mathematical modelling of the hypothalamic pulse generator, the pituitary pulse decoder and the effects of LH and FSH on gonadal cells. • Numerical optimisation by performing parameter fitting and sensitivity analysis using combination of available experimental data sets to parametrise and validate model components. • Simplification of the sub-system models (as informed by sensitivity analysis) and again, training on system wet-lab data. • Computational methods that allow the generation of testable model predictions regarding the reproductive system and its components across the lifespan. Eligibility To be eligible for a fully-funded studentship, you must meet both the academic and residence criteria. For UK/EU nationals who meet the residency requirements outlined by the BBSRC, the studentship will cover funding for 4 years (48 months) as follows. These awards might be available to part-time students, but only in exceptional circumstances. It is recommended you speak to the lead supervisor prior to submitting an application. • a stipend at the standard Research Council UK rate; currently £14,777 per annum for 2018-2019 • research and training costs • tuition fees (at the standard Research Councils UK rate) • additional funds to support fieldwork, conferences and a 3-month internship Please refer to the regulations<http://www.legislation.gov.uk/uksi/2007/779/pdfs/uksi_20070779_en.pdf> or Annex 1 of the Research Council Training Grant Guide<https://www.ukri.org/files/legacy/publications/rcuk-training-grant-guide-pdf/> to confirm that you meet the residence criteria for a fully-funded studentship. Any further queries in relation to residency must be directed to the institution that you are applying to. Entry requirements Applicants should have obtained, or be about to obtain, a First or Upper Second Class UK Honours degree, or the equivalent qualifications gained outside the UK, in an appropriate area of science or technology. Applicants with a Lower Second Class degree will be considered if they also have Masters degree or have significant relevant non-academic experience. In addition, due to the strong mathematical component of the taught course in the first year and the quantitative emphasis in our projects, a minimum of a grade B in A-level Maths or an equivalent qualification or experience is required. If English is not your first language you will need to have achieved at least 6.5 in IELTS and no less than 6.5 in any section by the start of the project. Alternative tests may be acceptable, please see http://www.bristol.ac.uk/study/language-requirements/profile-c/. Students from EU countries who do not meet the residency requirements may still be eligible for a fees-only award but no stipend. Applicants who are classed as International for tuition fee purposes are not eligible for funding. Please refer to the regulations<http://www.legislation.gov.uk/uksi/2007/779/pdfs/uksi_20070779_en.pdf> or Annex 1 of the Research Council Training Grant Guide<https://www.ukri.org/files/legacy/publications/rcuk-training-grant-guide-pdf/> to confirm that you meet the residence criteria for a fully-funded studentship. The four universities have a very limited number of fully-funded 4 year studentships that EU nationals who do not meet the residency requirements would be eligible for. Please contact us for for more information. How to apply Apply now Please be aware you will be asked to upload the following documents: * CV * Letter of application outlining your academic interests, prior research experience and reasons for wishing to undertake the project. Please indicate your preferred project choice if applying for multiple BBSRC SWBio DTP projects. * Transcript(s) giving full details of subjects studied and grades/marks obtained. This should be an interim transcript if you are still studying. * Two academic referees - see information below about references. * If you are not a national of a majority English-speaking country you will need to submit evidence of your proficiency in English (see entry requirements above) The closing date for applications is midnight on Monday, 3 December 2018. Interviews will be held at the University of Exeter on 7 and 8 of February 2019. Reference information You will be asked to name 2 referees as part of the application process, however we will not expect receipt of references until the shortlisting stage. Your referees should not be from the prospective supervisory team. If you are shortlisted for interview, please ensure that you two academic referees email their references to the pgrenquiries@exeter.ac.uk<mailto:pgrenquiries@exeter.ac.uk>, 7 days prior to the interview dates. Please note that we will not be contacting referees to request references, you must arrange for them to be submitted to us by the deadline. References should be submitted by your referees to us directly in the form of a letter. Referees must email their references to us from their institutional email accounts. We cannot accept references from personal/private email accounts, unless it is a scanned document on institutional headed paper and signed by the referee. If you have any general enquiries about the application process please email pgrenquiries@exeter.ac.uk<mailto:pgrenquiries@exeter.ac.uk>. Project-specific queries should be directed to the primary supervisor. Selection process: Please note, the studentship selection process will take place in two stages: 1. The project supervisors will consider your application and may invite you to visit for an informal interview. You can apply for more than one BBSRC SWBio DTP project, although supervisors may take into account your interest and commitment to their particular project. If you apply for multiple projects, please indicate your preferred project choice in your letter of application. Each application for an individual project will be considered separately by the project supervisors. 2. After closure of applications, each supervisory team will then nominate their preferred applicant. A shortlist will be selected from these nominations and shortlisted applicants will be invited for interview on a selection day at the University of Bristol. Please note that nomination by a project supervisor therefore does not guarantee the award of a studentship. Data Protection During the application process, the University may need to make certain disclosures of your personal data to third parties to be able to administer your application, carry out interviews and select candidates. These are not limited to, but may include disclosures to: * the selection panel and/or management board or equivalent of the relevant programme, which is likely to include staff from one or more other HEIs; * administrative staff at one or more other HEIs participating in the relevant programme. Such disclosures will always be kept to the minimum amount of personal data required for the specific purpose. Your sensitive personal data (relating to disability and race/ethnicity) will not be disclosed without your explicit consent. Summary Application deadline: 3rd December 2018 Value: Tuition fees and an annual stipend allowance at Research Council rates, currently £14,777 per year for 2018-19 Duration of award: per year Contact: PGR Recruitment Office pgrenquiries@exeter.ac.uk<mailto:pgrenquiries@exeter.ac.uk>