Supervisors: Dr. Androniki Psifidi, Prof. David Connolly, Prof. Virginia Luis Fuentes, Dr. Ankit Hinsu 

Department: Clinical Science and Services 

Project Details

Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease in humans and cats affecting up to 15% of the domestic cat population. Similar to HCM in human, feline HCM is characterised by thickening of the left ventricular myocardium leading to reduced cardiac function; clinical symptoms include arrhythmia, thromboembolism, heart failure and sudden cardiac death. However, in many cases of HCM, cats never exhibit clinical signs of cardiac disease (ie have subclinical disease) and can live a normal lifespan. HCM has an increased prevalence in certain cat breeds including Persian, British Shorthairs, Birman, Sphynx and Bengals indicating the role of genetics in the disease process. Previous studies have associated more than 1000 mutations in humans with HCM while, only handful have been detected in the cats despite the higher disease prevalence. Recent studies from our group and others suggest that HCM is a complex and heterogeneous disease and as such, the regulatory genome may play an important role in the development and progression of the disease. 

While previous studies have examined the role of genetic variants, we hypothesized that expression of long non-coding RNAs (lnc-RNAs) also plays an important role in HCM susceptibility and progression. Lnc-RNAs are non-coding RNA molecules greater than 200 nucleotides in length with limited or no protein-coding potential. These molecules interact with various cellular components, including DNA, RNA, and proteins, modulating gene expression at multiple levels – transcription, splicing, and translation. Lnc-RNAs play crucial roles in a wide range of biological processes, including cell development, cell differentiation, metabolism, and immunity. Several lnc-RNAs that play a role in the pathogenesis of human HCM have already been identified, but relevant studies are absent from the feline literature. In this project we aim to investigate for the first time the transcriptional landscape of HCM in cats with a focus on the role of lnc-RNAs in the disease. 

The current study will focus on the expression levels of lnc-RNAs in the left ventricular myocardium of healthy and HCM affected cats. To date we have already collected appropriate myocardial samples form carefully phenotyped control and HCM affected cats using echocardiography. Additionally, total RNA from the tissue samples has already been sequenced using Illumina technology. The MRes student will be using the existing dataset to identify the lnc-RNAs from the total RNA data and then characterize the differential expression of lnc-RNAs between healthy and affected cats using relevant bioinformatic tools and software.  The protein coding genes that are targeted by these lnc-RNAs will be also identified. The key candidate genes and lnc-RNAs will also be validated using Real-time RT-PCR and other methods. The successful candidate will develop cutting edge bioinformatics and wet-lab skills. This project will evaluate the potential involvement of lnc-RNAs in feline HCM and may identify novel disease biomarkers and therapeutic targets. 

References

1. M.D. Kittleson, K.M. Meurs, S.P. Harris. The genetic basis of hypertrophic cardiomyopathy in cats and humans. Journal of Veterinary Cardiology 2015; 17, S53-S73. DOI: 10.1016/j.jvc.2015.03.001 

2. J. Joshua, J. Caswell, M.L. O’Sullivan, G. Wood, S. Fonfara. Feline myocardial transcriptome in health and in hypertrophic cardiomyopathy—A translational animal model for human disease. PLoS ONE 2023; 18(3), e0283244. DOI: 10.1371/journal.pone.0283244 

Requirements

Essential:

• Must meet our standard MRes entry requirements.
• The student doesn’t need to be a veterinary graduate. 

Desirable:

• Previous experience of statistical analysis and use of R would be desirable but not essential.  
• Previous wet-lab experience would be also desirable.  

This can be taken full-time or part-time (12months FTE) project commencing in October 2024, based at RVC's Hawkshead campus. 

Funding

Partially funded: The total RNA Seq data and wet-lab consumables haveas been already generated through a Petplan Charitable Trust funded project. The MRes student will be expected to meet the course fees and their living expenses. 

International applicants are welcome to apply but must be able to fund the difference between "Home" and "Overseas" tuition fees. Please note that EU/EEA and Swiss national students may no longer be eligible for the “Home” rate of tuition fees, dependent on personal circumstances (including immigration status and residence history in the UK) and UK government rules which are currently being developed. For up-to-date information on fees for EU/EEA and Swiss national students following Brexit please see our fees and funding page. 

How to Apply

For more information on the application process and English Language requirements see How to Apply.

Deadline: Sunday 14th July 2024

We welcome informal enquiries - these should be directed to Dr. Androniki Psifidi (apsifidi@rvc.ac.uk)

Interview date and location: TBC