Cardioimmunology: Dissecting immune mechanisms underlying infection-driven heart disease.

Cardiovascular diseases are the leading cause of death globally. The immune system, our body’s way of protecting us from infections, plays a key role in cardiac development, composition, and function. Under some circumstances, particularly in response to infection, immune cells can infiltrate the heart in large numbers to remove dying tissue, scavenge pathogens and promote healing. If uncontrolled, these immune cells can cause collateral tissue damage, leading to heart dysfunction and failure.

The goal of this PhD programme is to better understand the immune mechanisms that contribute to heart tissue damage in response to infection.

For this, we will use Trypanosoma cruzi as an infection model. T. cruzi is the protozoan parasite that causes Chagas disease (American trypanosomiasis), the leading cause of infectious heart disease worldwide and the highest-impact parasitic disease in the Western Hemisphere.     

Using spatial transcriptomics, our team has identified a diverse immune cell infiltrate dominated by B cells in hearts from T. cruzi-infected mice. Originally recognised as white blood cells that produce antibodies, B cells have been shown to play much broader roles, particularly orchestrating and modulating the immune response.

The successful candidate will combine cutting-edge transcriptomics and proteomics with transgenic mouse models to further dissect the role of immune cells infiltrating the heart during T. cruzi infection. By the end of the PhD, the candidate will have made significant discoveries in the field of cardioimmunology. The candidate will graduate with a clear understanding of mouse models of immunity and infection, cutting-edge molecular immunology technologies, as well as strong laboratory and transferrable skills. Further, the candidate will manage their own small research budget and will further be encouraged to apply for additional external funding and write original research papers .

For informal inquiries, please contact Dr. Damian Perez Mazliah, [Email Address Removed]

Location and Research Culture

The student will join on a full time basis a young and dynamic research team (Perez Mazliah lab) part of the Experimental Medicine and Biomedicine group at Hull York Medical School at the University of York. The student will be further co-supervised by Professor Paul Kaye.

Hull York Medical School is a unique partnership bringing together the expertise of both the Universities of Hull and York and offering a thriving environment in which to conduct world-leading research. Strong partnerships with NHS Trusts and community health organisations offer a wide clinical base that fosters translation of biomedical research to improve health. Our research is a key component of the York Biomedical Research Institute.

You will be part of a vibrant post-graduate community within the medical school but also interacting with students from other PhD Programmes at the University of York. You will have access to the University of York Biosciences Technology Facility, allowing the use of cutting-edge equipment to support the research as needed for the project (e.g. imaging, bioinformatics etc.) You will be supported by a thesis advisory panel and will follow a training programme on transferable and research skills.

Our Department of Health Science’s (Hull York Medical School, Centre for Health Economics, Centre for Reviews and Dissemination) academic and clinical researchers have a strong reputation for their work, with over 92% of our research classed as ‘world-leading’ (REF 2021). Our research is advancing improvements in healthcare – treatment, diagnosis and care – improving the health of people locally and impacting national and international health agendas in areas such as neglected tropical diseases, cancer research, palliative medicine, mental health and global public health.

Funding

·        A 4-year stipend paid at RCUK rates (currently £17,668 per annum in 22/23)

·       Funding to cover UK PhD fees (International students will need to fund the difference between home and overseas fee rates)

·       £24K research expenses

References

Host-parasite dynamics in Chagas disease from systemic to hyper-local scales, Parasite Immunology, 2021

https://onlinelibrary.wiley.com/doi/full/10.1111/pim.12786

Plasmodium-specific atypical memory B cells are short-lived activated B cells, eLife, 2018

https://elifesciences.org/articles/39800

Additional suggested readings

New perspectives of the cardiac cellular landscape: mapping cellular mediators of cardiac fibrosis using single-cell transcriptomics

https://portlandpress.com/biochemsoctrans/article-abstract/48/6/2483/227085/New-perspectives-of-the-cardiac-cellular-landscape?redirectedFrom=fulltext

Spatiotemporal transcriptomics reveals pathogenesis of viral myocarditis

https://www.nature.com/articles/s44161-022-00138-1

Start Date

1^st October 2023

Qualification Required

In order to qualify for this scholarship you will require an undergraduate degree with at least a 2.1, or equivalent, in a relevant subject. English Language IELTS 6.5 with a minimum of 6.0 in each component.

We are looking for an energetic, enthusiastic and intelligent PhD candidate, with the ability to plan and take responsibility for own work. This will be a very demanding yet rewarding PhD programme. Previous hands-on experience with single-cell RNA sequencing, mouse work, flow cytometry, microscopy and or cryosectioning, as well as solid background knowledge in Immunology will be an advantage.

How to Apply

Applications MUST BE submitted to Hull York Medical School via the online application method choosing option PhD in Medical Sciences, 2023 October, full-time:

https://www.york.ac.uk/study/postgraduate/courses/apply?course=DRPMEDSMED3&level=postgraduate

The deadline for applications is 26^th May 2023

In order for the Panel to get a sense of your academic background, commitment and interest, you are required to complete the application form in full and provide a research proposal/outline of academic interest. Research proposals and personal statements may be used in selecting applicants for interview. If you have any queries on how to apply please email [Email Address Removed].

As part of the admissions process you are required to provide the following documentation. The more information you provide, the more comprehensive your application would be for the Panel to consider.

•  Academic transcripts showing qualification

•  Evidence of English language ability (for non-native speakers)

•  References

•  Curriculum Vitae

•  Written Work

Please note that this is a student scholarship. If you will be employed by HYMS (e.g. on a fixed or short term contract) for the duration of your study, you will not be eligible to receive the student scholarship as a member of HYMS staff. 

Interviews

Interviews will take place online during the second week of June. Applicants who are shortlisted for interview will be contacted via email. Please note that we do not offer feedback to applicants who are not invited to the interview.