Gene-mediated differentiation of mesenchymal precursor cells for the identification of novel morphogenic gene therapeutics

Project description

The successful induction of cellular differentiation for regeneration via gene therapy depends on the identification of suitable therapeutic genes. Ideally, such genes could be selected from panels inspired by developmental signalling of the target tissue type.

Cellular differentiation & multi-lineage potency have been shown to be controlled by specific factors and cues, which were originally identified in developmental biology. Non- viral gene therapy in regenerative medicine could significantly benefit from the identification of novel therapeutic genes or gene combinations that encode specific morphogenic signals.

This project aims at screening a panel of therapeutic genes, which are selected from relevant developmental pathways, in clinically relevant precursor cells in vitro to study induced changes in differentiation/phenotype and marker gene expression for the development of next-generation gene therapeutics in regenerative medicine.

It represents a combination of discovery and applied science, necessary for fundamental science discovery and the development of novel therapies resonating with identified priority areas within the health theme of the University. This project will deliver a competitive edge in regenerative medicine to enable excellent world leading research with the potential to be translated from bench to patient to population. The project outputs will help to innovate and transform global health and quality of life contributing to the world leading research excellence demonstrated by the School of Dentistry in musculoskeletal health.

Aims and objectives:

Aim: Identification of therapeutic genes from relevant developmental pathways in clinically relevant precursor cells in vitro for the development of next- generation gene therapeutics for developmental engineering in regenerative medicine.

Objectives:

  1. Cloning & Expression of relevant morphogenic transgenes and design & evaluation of eukaryotic expression vectors.
  2. Characterisation of gene & gene-combination induced differentiation in reporter cell lines and mesenchymal precursor cells using reporter gene assays and differentiation-specific qPCR assays.

References:

  1. Occhetta, P., et al., Developmentally inspired programming of adult human mesenchymal stromal cells toward stable chondrogenesis. Proc Natl Acad Sci USA, (2018) 115(18): 4625-4630.
  2. Tonnarelli, B., et al., Re-engineering development to instruct tissue regeneration. Curr Top Dev Biol, (2014) 108: 319-38.
  3. Feichtinger, G.A., et al., Constitutive and inducible co-expression systems for non-viral osteoinductive gene therapy. Eur Cell Mater, (2014) 27: 166-84; discussion 184.
  4. Feichtinger, G.A., et al., Sonoporation Increases Therapeutic Efficacy of Inducible and Constitutive BMP2/7 In Vivo Gene Delivery. Hum Gene Ther Methods, (2014) 25(1): 57-71.

Entry requirements

A PhD studentship is available for UK and EU citizens only. The studentship will attract an annual tax-free stipend of £14,777 for up to 3 years, subject to satisfactory progress and will cover the UK/EU tuition fees. 

You should hold a first degree equivalent to at least a UK upper second class honours degree in a relevant subject. This project would suit a student with a biological background.

Candidates 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 minimum requirements are:

•      British Council IELTS - score of 6.5 overall, with no element less than 6.0

•      TOEFL iBT - overall score of 92 with the listening and reading element no less than 21, writing element no less than 22 and the speaking element no less than 23.

How to apply

To apply for this scholarship applicants should complete a Faculty Scholarship Application form 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 fmhgrad@leeds.ac.uk

We also require 2 academic references to support your application. Please ask your referees to send these references on your behalf, directly to fmhgrad@leeds.ac.uk by no later than Friday 29 March 2019.

If you have already applied for other scholarships using the Faculty Scholarship Application form you do not need to complete this form again. Instead you should email fmhgrad@leeds.ac.uk to inform us you would like to be considered for this scholarship project.

Any queries regarding the application process should be directed to fmhgrad@leeds.ac.uk 

How to apply (email)

fmhgrad@leeds.ac.uk