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Impact of clonal haematopoiesis on ventricular remodelling after myocardial infarction: establishing high throughput screening for translatable therapeutic targets

Subject areas:

Cardiovascular, heart failure, myocardial infarction, molecular biology, inflammation, immunology.

Funding type:

Stipend. Study costs. Bench Fees / Research Training & Support Grant.

Country:

Home Fee Status Students.



Investigate whether DNMT3A clonal haematopoiesis driver mutations which result in worse recovery after myocardial infarction, can be therapeutically targeted using high-throughput screening approaches

Award details

This PhD project aims to address the critical challenge of heart failure (HF) following myocardial infarction (MI), a leading cause of morbidity and mortality globally, especially among individuals under 60. The project seeks to investigate the role of clonal haematopoiesis (CH), a novel risk factor for HF characterised by the acquisition of mutations in haematopoietic cells, which drive dysfunctional inflammatory responses contributing to adverse cardiac remodelling post-MI.

The objectives of the PhD are: 1) To optimize a high-content, high-throughput RNA interference (RNAi) screening to identify CH-driven signalling pathways that mediate deleterious changes in mutant human-derived cells; and 2) To perform multimodal target validation studies, including pharmacological validation.

Principle techniques will include cell culture and screening. Here, cells will be isolated from a biobanked cohort and subjected to RNAi screening using the Opera Phenix High-Content Screening System to investigate gene functions during immune activation. Target validation will be performed using a combination of in vitro and in vivo assays, including cytokine profiling and phenotypic analysis of immune cell migration and phagocytosis.

This project will provide critical insights into the pathophysiological role of CH in cardiac remodelling post-MI. The project aims to contribute to the discovery of novel therapeutic targets that could mitigate the progression to HF, particularly focusing on personalised medical approaches that could rapidly translate into clinical settings. This work will enhance our understanding of HF pathogenesis and support the development of targeted therapies that address the underlying genetic and molecular causes of post-MI HF. 

The project will be hosted at King’s College London, with access to cutting-edge facilities and a supervisory team possessing extensive experience in cardiovascular medicine, clinical studies, and translational research. This environment ensures an excellent foundation for undertaking this innovative research project.

Start date: June 2025

Duration: 3.5 years

Sponsor: Kusuma Trust

For enquiries please contact SCMMS-PGR@kcl.ac.uk 

 

Award value

Stipend: BHF rates

Bench Fees: Bence fees relevant to the project will be provided.

Tuition Fees: Home tuition fees will be fully covered by this award.

Eligibility criteria

The programme is open to Home fee status students only. The programme welcomes applications from a diverse range of backgrounds. Applicants will be reviewed on qualifications, experience and potential to undertake a research degree.

To be eligible for consideration applicants must possess, or be expected to achieve, a 1st or high upper 2nd class degree (or equivalent) in a biomedical science subject. Applications from students with a relevant Masters’ degree are also welcome.

English Language Requirements:

If English is not your first language you will be required to provide evidence that you meet the minimum English requirements of the Faculty details can be found on our website. If you are unable to provide this confirmation before applying any offer you are made would be conditional upon you meeting these requirements prior to enrolment and no later than 4 weeks before the course starts

Application process

To apply, please visit the King’s Apply website and follow the steps outlined below.

  • Register a new account and login.
  • Open a new application.
  • Select the programme:
  1. Select ‘Research programmes’
  2. Enter ‘Cardio’, then Search
  3. Select: ‘Cardiovascular Medicine and Science Research MPhil/PhD (Full-time)’. Your application cannot be considered if submitted under the incorrect programme.
  • Complete and submit your application noting the following:
  1. Include a supporting personal statement, no project proposal is needed.
  2. 2 References
  3. CV
  4. Funding – select drop-down ‘4. Grant Awarding Body’. For the award status, select 'Advertised Scholarship' and in the box marked ‘Ref No.:’, please enter: ‘KU25’.

 
 

Academic year:

2024-25

Study mode:

Postgraduate research

Application closing date:

03 March 2025