Postgraduate research

Health Inequalities in Leicester: The influence of maternal, perinatal and neonatal factors on neonatal T cell and Innate Lymphoid Cell (ILC) immune function and epigenetics

Qualification: PhD

Department: Respiratory Sciences

Application deadline: 6 Janaury 2023

Start date: 1 March 2023

Overview

Supervisors

Project description

Aim

To explore key aspects of T lymphocyte and ILC function and their epigenetics, in late pre-term and early term (LPET) births in Leicester. This will be done in the context of key epidemiological factors known or hypothesised to be associated with epigenetic variation in immune gene expression. 

Rationale

The neonatal innate and adaptive immune system faces unparalleled challenges after birth: a) immediate exposure to and colonisation by microbes leading to development of a diverse microbiome; b) developing sufficient tolerance to this allogeneic challenge; c) differentiating this from pathogens, to which they must mount an adequate immune response. 

Cells such as IL-8 producing T cells and regulatory T cells are important in fine-tuning levels of immune reactivity and tolerance to accommodate these developmental needs in neonates. More recent identification of innate lymphoid cells (ILCs) as part of a complex matrix of cellular pathways regulating mucosal immunity is also likely to be relevant in the developing neonatal immune system. Mounting evidence suggests prenatal, perinatal and postnatal exposures such as maternal smoking, obesity and fetal nutritional deficiencies can potentially alter ‘epigenetic profiles’ that define the expression of genes associated with this immunity and, potentially, the immune responses that exposed individuals mount.

Leicester experiences higher rates of neonatal mortality, infant mortality, preterm birth and low birth weight compared to the whole of England. Known risk factors include maternal smoking, maternal obesity and intrauterine growth restriction, all of which are higher in Leicester.  It is plausible that, amongst associations with higher infant mortality and morbidity in the region, links may exist to variations in immune responses driven by locally prevalent epigenetic influences, or to other factors associated with the immune response. 
This research will add new information to either support or refute the hypothesis that an association exists between health inequalities and immune function in early life. 

The study will be aligned to the LCFC Research Programme in Child Health, and nested within a cohort study of LPET births. These represent a large, but under-researched population with increased rates of respiratory, cardiovascular, and metabolic health issues across the whole lifespan. 

Methodology

Cohort: LPET births at University Hospitals Leicester NHS Trust (UHL), whose parents offer consent for participation in the study.

Sample size: 200 LPET mother baby dyads. 

Samples: Umbilical cord blood and neonatal blood samples will be collected in EDTA tubes. Peripheral blood mononuclear cells (PBMCs) will be separated and stored at -70 degrees in the Cousins laboratory at University of Leicester. Samples will be analysed at the Cousins laboratory using the flow cytometry core facility. We will also collect placental samples for analysis.

Analysis: T cell and ILC multicolour flow cytometry using appropriate cell markers and functional studies will be conducted by the PhD student. 

Epigenetic studies will be performed in collaboration with Dr Deena Gibbons (KCL), who has extensive experience of analysis of T-cell function in neonates.

Funding

Funding

Funding source: Leicester City Football Club

This 3-year PhD Studentship provides:

  • UK tuition fee waiver

  • Annual stipend at UKRI rates (£17,668 for 2022/23)

Entry requirements

Entry requirements

Applicants must hold a UK Bachelor's degree with at least a 2:1 (or overseas equivalent) in a relevant subject area.

University of Leicester English language requirements apply (where applicable)

Informal enquiries

Informal enquiries

Project enquires

Application enquiries

How to apply

How to apply

To submit your application, please use the 'Apply' button at the bottom of the page and select May 2023 from the dropdown menu.

Include the following with your application:

  • CV
  • Personal statement (max 1000 words) explaining your interest in the project, your experience and why we should consider you
  • Degree Certificates and Transcripts of study already completed and if possible transcript to date of study currently being undertaken
  • Evidence of English language proficiency if applicable
  • In the reference section please enter the contact details of your two academic referees in the boxes provided or upload letters of reference if already available.
  • In the funding section please specify that you wish to be considered for the Leicester City Football Club Studentship
  • In the research proposal section please provide the names of the project supervisors and the project title (a proposal is not required)

Eligibility

Eligibility

UK (Home) applicants only

*Applicants holding EU Settled and Pre-Settled status, we will require a UK government share code so that we can verify your status (The share code we require starts with S)  please email your share code together with your application ID to pgradmissions@leicester.ac.uk  once you have submitted your PhD application.

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