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School of Engineering and Materials Science Research Studentships

Nanobioarrays to screen for modulators of mechanosensing in heart failure

Supervisors: Thomas ISKRATSCH

Application Deadline: 30-01-2022

Heart failure (HF) is a major cause of death in the UK. New therapies are urgently needed but their development has been hindered by the still limited understanding of the biological basis. Apart from genetic and humoral factors, the mechanical/physical signals are critically involved in the process.

Especially, the cardiac extracellular matrix (ECM) stiffens in heart disease, which drives disease progression. However, not only the stiffness, but also changes in ECM composition will alter the downstream mechanosignalling. Better understanding of the mechanobiology can open new perspectives for treating heart failure. Therefore, novel tools are needed to help understand the complexity of both stiffness and receptor ligand architecture in heart disease.

We previously investigated cardiomyocyte mechanosensing (Pandey et al, Developmental Cell, 2018) and adhesion formation, for which we developed biomimetic nanoarrays (here: nanobioarrays), based on nanopatterned DNA origami (Hawkes et al, Faraday Discussions, 2019). Using our new NanoFrazor Explore thermal-scanning probe lithography tool, we are now able to pattern on surfaces with different stiffness. This way we can generate next-generation nanobioarrays to enable quantitative measurement of changes to adhesion composition in response to the precisely defined presence and relative abundance of specific receptor ligands, as well as the stiffness of the environment. Especially, we seek here to develop nanobioarrays with tunable stiffness and different ratios of integrin ligands for extracellular matrix components that are present in the healthy and diseased myocardium in order to study the implications on downstream adhesion signalling and identify druggable modifiers of the mechanosignalling. For this the student will:

  1. Develop next-generation nanobioarrays with tunable stiffness and defined integrin ligand configuration
  2. Analyse the adhesion composition depending on stiffness and receptor ligand configuration
  3. Analyse the mechanosignalling (e.g. active integrin, pSrc, pFAK, YAP, etc) depending on stiffness and receptor ligand configuration
  4. Screen for modulators of mechanosignalling

Funding

This studentship is fully funded via the UKRI EPSRC Doctoral Training Programme for 3.5 years and includes a stipend (currently £17,609 in 2021/2022) and Fees.

Eligibility

This year UKRI announced that there will be a limited number of studentships for international students available.  International applicants are encouraged to apply but should note that studentship awards will be subject to eligibility and the availability of funding.

To be classed as a home student, applicants must meet the following criteria:

  • Be a UK National (meeting residency requirements), or
  • Have settled status, or
  • Have pre-settled status (meeting residency requirements), or  
  • Have indefinite leave to remain or enter

If a candidate does not meet the criteria above, they would be classified as an international student.

Further guidance on UKRI Eligibility Criteria is here, and within Annex One of the International Eligibility Guidance.

  • The minimum requirement for this studentship opportunity is a good Honours degree (minimum 2(i) honours or equivalent) or MSc/MRes in a relevant discipline.
  • If English is not your first language, you will require a valid English certificate equivalent to IELTS 6.5+ overall with a minimum score of 6.0 in Writing and 5.5 in all sections (Reading, Listening, Speaking).
  • Candidates are expected to start from September 2022

Supervisor Contact Details:

For informal enquiries about this position, please contact Dr Thomas Iskratsch, E-mail: t.iskratsch@qmul.ac.uk

Application Method:

To apply for this studentship and for entry on to the PhD Full-time Medical Engineering - Semester 1 (September Start) please follow the instructions detailed on the following webpage:

Research degrees in Engineering:‚Äč http://www.qmul.ac.uk/postgraduate/research/subjects/engineering.html

Further Guidance: http://www.qmul.ac.uk/postgraduate/research/

Please be sure to include a reference to ‘2022 EPSRC DTP TI’ to associate your application with this studentship opportunity.

Website: http://www.qmul.ac.uk/postgraduate/research/subjects/engineering.html