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Nanoparticle based delivery to the heart


Project Description

Project Description
The Midlands Integrative Biosciences Training Partnership 3 (MIBTP2020) is a BBSRC-funded doctoral training partnership between the University of Warwick, University of Birmingham, University of Leicester, Aston University and Harper Adams University recruiting students for four-year studentships starting in Oct 2020. This innovative, interdisciplinary research training programme offers the opportunity to undertake a PhD in the fundamental understanding of, and application of functional nanomaterials to societal challenges, including energy, health, or emerging technologies.

SUPERVISORY TEAM
Lead supervisor: Prof Rachel O’Reilly (School of Chemistry)
Co-supervisors: Dr Katja Gehmlich (MDS, Institute of Cardiovascular Sciences) and Dr Amanda Pearce (School of Chemistry)
THE PROJECT
Healthy ageing in the Western world relies on healthy diet, sufficient exercise and avoiding risk factors such as smoking, alcohol consumption or environmental stressors, but is partly also defined by the genetic setup of an individual. For the majority of people, co-morbidities emerge with age. One prime example for an age-related cardiac co-morbidity is atrial fibrillation (AF), the most common cardiac arrhythmia. AF is prevalent in the aging population (affecting 7 in 100 over 65 years) and associated with a high risk of stroke and development of heart failure.
Insights into the molecular mechanisms of AF in pre-clinical studies have led to the identification of potential preventative agents, such as the inhibition of Ca2+ /calmodulin-dependent protein kinase II (CamKII). However, targeting of this enzyme appears currently not a viable preventative option, as inhibition of CamKII has detrimental effects on the brain and its memory functions. Specific targeting of CamKII inhibitors to the heart, but not to the brain, would be a pre-requisite for exploring CamKII inhibition as a therapeutic option for AF.
The aim of this studentship is therefore to engineer nanoparticles [3] allowing specific delivery of preventative agents to the heart. To achieve this, the student will work with an interdisciplinary team of supervisors consisting of chemists and a biologist, using world-class facilities at the University of Birmingham. Nanoparticles will be synthesised in the School of Chemistry and cardiomyocyte specificity achieved through the display of peptides, mimicking ligands which interact with cardiomyocyte-specific surface receptors. Cargos will initially include reporter genes or dyes and will evolve to therapeutic agents in the later stages of the project.
The efficient targeting of nanoparticles will be tested in cardiac in vitro systems, making use of mouse primary atrial and ventricular cardiomyocytes and human induced pluripotent stem cell derived cardiomyocytes. This work will take place in the Institute of Cardiovascular Sciences.
In the later stages of the project, the potential benefits of nano-particle delivery for preventative agents (e.g. CamKII inhibitors) will be assessed in a cellular model system of arrhythmia, making use of genome-edited induced pluripotent stem cell derived cardiomyocytes and electrophysiological read-outs.
During the project, the PhD student will develop skills in research and writing literature; developing and characterising nanoparticles; tissue culture techniques to test the in vitro efficacy of the technology in physiologically relevant environments. Techniques likely to be used during the PhD include small molecule synthesis; nanoparticle preparation; chemical characterisation; dynamic light scattering; tissue culture and microscopy.
We are looking for a motivated and enthusiastic applicant with a willingness to engage in interdisciplinary and translational research. The studentship is open to applicants from a range of backgrounds (e.g. biology, chemistry, engineering).
For more information and to apply please visit: https://warwick.ac.uk/fac/cross_fac/mibtp/pgstudy/phd_opportunities/

Residence requirements for MIBTP studentships:

British nationals who have lived in the UK all their lives are eligible.

Also eligible are non-British nationals who have settled status AND have been resident in the UK for 3 years immediately prior to the date of the start of the course.

EU nationals who have been ordinarily resident in the UK and Islands for three years immediately prior to the date of start of the course are eligble.

EU nationals who have been ordinarily resident in an EU country (other than the UK) for three years immediately prior to the date of start of the course are eligble for matched funding studentships only (a fees only award from BBSRC with the remainder topped up by the University to equal a full studentship).

EEA and Swiss nationals (EEA migrant workers) should refer to the full guidelines to check eligibility.

UK / EU nationals who have been living outside of the UK within the three years immediately prior to the date of start of the course may not be eligible for a studentship. Please refer to the guidelines for clarification.

How good is research at University of Birmingham in Chemistry?

FTE Category A staff submitted: 28.00

Research output data provided by the Research Excellence Framework (REF)

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