One of the key engineering challenges in the life-science and biomedical sectors is the design and manufacturing of bespoke scaffolds for 3D cell culture, tissue engineering and cell/drug delivery, i.e. cell niches. These cell niches underpin a large and growing sector of biotech and biomed industries whether they are used (i) in-vitro for the study of cell behaviour, toxicity testing or tissue engineering, or (ii) in-vivo for the delivery of cells and/or drugs or to promote regeneration of damaged tissues.
In this context the development of in-vitro cardiac models has been the focus of significant work both from engineers and biologists, to understand the developmental biology and disease development of this key organ. In addition, these models are also highly relevant to drug toxicity testing, as heart failure is one of the key side effects of a number of current drugs, and in particular of chemotherapies linked of the treatment of cancer.
Through this project we aim to bring together through an interdisciplinary collaboration two recent technological advances made by Profs Saiani and Keavney groups in the field of 3D cell niche formulation and design, and cardiac cell co-culture, to develop a novel synthetic peptide-based in-vitro cardiac model.
Using co-culture methods of cell lineages differentiated from human embryonic stem cells, the Keavney group have generated a novel cardiac organoid platform incorporating the three major cell types involved in heart development. In this project, you will further develop this model by incorporating peptide hydrogels developed by the Saiani group. You will assess the effect of different hydrogel formulations on cellular maturity and phenotype (eg gene expression profiling, spontaneous beating, expression of functional ion channels, development of morphological structures). When the model is optimised (target: end of year 2), you will test the effect of genetic variants shown by the Keavney group and others to affect heart development and predispose to congenital heart disease. You will also test the effects of known teratogens which predispose to congenital heart disease, and investigate the molecular mechanisms whereby these teratogenic effects occur.
Prof A. Saiani
http://www.polymersandpeptide.com Prof B. Keavney
http://www.keavneylab.com twitter: @keavneylab
Entry Requirements:
Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.
UK applicants interested in this project should make direct contact with the Principal Supervisor to arrange to discuss the project further as soon as possible. International applicants (including EU nationals) must ensure they meet the academic eligibility criteria (including English Language) as outlined before contacting potential supervisors to express an interest in their project. Eligibility can be checked via the University Country Specific information page (
https://www.manchester.ac.uk/study/international/country-specific-information/).
If your country is not listed you must contact the Doctoral Academy Admissions Team providing a detailed CV (to include academic qualifications – stating degree classification(s) and dates awarded) and relevant transcripts.
Following the review of your qualifications and with support from potential supervisor(s), you will be informed whether you can submit a formal online application.
To be considered for this project you MUST submit a formal online application form - full details on how to apply can be found on the BBSRC DTP website
http://www.manchester.ac.uk/bbsrcdtpstudentships
