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The role of NLRP family proteins in the development of the oocyte and preimplantation embryo.

PGR-P-184

Key facts

Type of research degree
4 year PhD
Application deadline
Ongoing deadline
Country eligibility
International (outside UK)
Funding
Non-funded
Supervisors
Dr John Huntriss and Professor Helen Picton
<h2 class="heading hide-accessible">Summary</h2>

NLRP proteins (Nucleotide-binding oligomerization domain, Leucine rich Repeat and Pyrin domain containing Proteins) are members of the NLR (Nod-like receptors) protein family. NLRPs are expressed abundantly in mammalian oocytes. For example, NLRP5 (also known as MATER-maternal antigen that embryos require) is a key protein within the mammalian subcortical maternal complex (SCMC), a multiprotein complex uniquely expressed in mammalian oocytes and early embryos that has multiple functions including spindle formation, positioning of the meiotic spindle, the regulation of translation, and epigenetic reprogramming of early embryos [1]. Notably, NLRP5 is essential for epigenetic regulation, since in humans, mutations in the NLRP5 gene have been associated with reproductive wastage and Multilocus Imprinting Disturbance (MLID) [2]. NLRP5 is also essential for early embryo development in other mammals [3,4] and appears to be involved in a number of important processes in the oocyte, including a potential role in the formation of the cytoplasmic lattice (CPL), an essential structure in the oocyte [5].

<h2 class="heading hide-accessible">Full description</h2>

<p>This PhD studentship aims to establish the precise role(s) of at least one member of the NLRP protein familyin the regulation of mammalian oogenesis and embryogenesis. The bovine reproductive model will be used as a model for understanding their role in epigenetic processes in humans. The favoured target is the NLRP5 gene. The functional impact of NLRP5 knock-down on epigenetic programming will be studied in the bovine oocyte and preimplantation embryo by knocking the gene down in oocytes using DsiRNAs. Changes in the oocyte and embryonic transcriptome and the embryonic DNA methylome will be assessed to reveal gene pathways and regions of the genome that are affected upon NLRP5 depletion. Embryonic development after knockdown will be assessed using for example, time-lapse techniques and/or other established metrics of embryo development. The project will also map the expression patterns of NLRP familytranscripts and proteins in bovine tissues, ovarian follicles, oocytes and preimplantation embryos.</p> <p>The student will receive training in a range of cellular and molecular techniques that are applicable across many themes in biomedical research. These include molecular biology, including transcriptome analysis (for example: real time PCR, cDNA library generation from single oocytes/embryos and single cells, RNA sequencing), DNA methylation analysis (for example: pyrosequencing, reduced representation bisulfite sequencing). In addition the student will be trained in techniques in reproductive biology, (for example: oocyte in vitro maturation (IVM), microinjection, in vitro fertilization (IVF) and preimplantation embryo culture). In summary, these experiments will attempt to dissect the role of NLRP proteins in mammalian oogenesis and preimplantation development.</p> <h3>References:</h3> <p>Bebbere D, Masala L, Albertini DF, Ledda S. The subcortical maternal complex: multiple functions for one biological structure? J Assist Reprod Genet. 2016 33(11):1431-1438.</p> <p>Docherty LE, Rezwan FI, Poole RL et al. Mutations in NLRP5 are associated with reproductive wastage and multilocus imprinting disorders in humans. Nat Commun. 2015 1;6:8086.</p> <p>Peng H, Liu F, Li W, Zhang W. Knockdown of NLRP5 arrests early embryogenesis in sows. Anim Reprod Sci. 2015 163:151-6.</p> <p>Maternal depletion of NLRP5 blocks early embryogenesis in rhesus macaque monkeys (Macaca mulatta). Wu X. Hum Reprod. 2009 24(2):415-24.</p> <p>Kim B, Kan R, Anguish L, Nelson LM, Coonrod SA. Potential role for MATER in cytoplasmic lattice formation in murine oocytes. PLoS One 2010 7;5(9):e12587.</p>

<h2 class="heading">How to apply</h2>

<p>Please note these are not standalone projects and applicants must apply to the PhD academy directly.</p> <p>Applications can be made at any time. To apply for this project applicants should complete a<a href="https://medicinehealth.leeds.ac.uk/downloads/download/129/faculty_graduate_school_-_application_form"> Faculty Application Form</a> and send this alongside a full academic CV, degree transcripts (or marks so far if still studying) and degree certificates to the Faculty Graduate School <a href="mailto:fmhpgradmissions@leeds.ac.uk">fmhpgradmissions@leeds.ac.uk</a></p> <p>We also require 2 academic references to support your application. Please ask your referees to send these <a href="https://medicinehealth.leeds.ac.uk/downloads/download/130/faculty_graduate_school_-_scholarship_reference_form">references</a> on your behalf, directly to <a href="mailto:fmhpgradmissions@leeds.ac.uk">fmhpgradmissions@leeds.ac.uk</a></p> <p>If you have already applied for other projects using the Faculty Application Form this academic session you do not need to complete this form again. Instead you should email fmhgrad to inform us you would like to be considered for this project.</p> <p>If English is not your first language, you must provide evidence that you meet the University&#39;s minimum English language requirements (below).</p>

<h2 class="heading heading--sm">Entry requirements</h2>

A degree in biological sciences, dentistry, medicine, midwifery, nursing, psychology or a good honours degree in a subject relevant to the research topic. A Masters degree in a relevant subject may also be required in some areas of the Faculty. For entry requirements for all other research degrees we offer, please contact us.

<h2 class="heading heading--sm">English language requirements</h2>

Applicants whose first language is not English must provide evidence that their English language is sufficient to meet the specific demands of their study. The Faculty of Medicine and Health minimum requirements in IELTS and TOEFL tests for PhD, MSc, MPhil, MD are: &acirc;&euro;&cent; British Council IELTS - score of 7.0 overall, with no element less than 6.5 &acirc;&euro;&cent; TOEFL iBT - overall score of 100 with the listening and reading element no less than 22, writing element no less than 23 and the speaking element no less than 24.

<h2 class="heading">Contact details</h2>

<p>For further information please contact the Graduate School Office<br /> e:<a href="mailto:fmhpgradmissions@leeds.ac.uk">fmhpgradmissions@leeds.ac.uk</a>, t: +44 (0)113 343 8221.</p>


<h3 class="heading heading--sm">Linked research areas</h3>