Biochemistry - Metabolic regulation of impaired cardiomyocyte biology using induced pluripotent stem cells

Supervisor: Dr Rachel Oldershaw

Supervisor bio: Dr Rachel Oldershaw is a stem cell biologist and a lecturer at the University of Liverpool. Her research is focused on the role of stem cells in the maintenance of tissue health and function and how impairment in stem cell biology contributes to the onset and progression of disease. Her research is also focused on how adult, embryonic and induced pluripotent stem cells can be used in the development of regenerative medicines that repair damaged tissues, with a focus on the musculoskeletal system, the eye and cardiac tissues.

Email: lrao1@liverpool.ac.uk

School: School of Biosciences 

Department: Biochemistry

Module code: LIFE398

Suitable for students of Biochemistry, Chemistry  

Desirable experience/requirements: N/A

Places available: 2

Start date: 16 June 2025 only

Project length: 4 or 8 weeks 

Virtual option: No

Project description: 

The isolation of cardiomyocytes from human cardiac tissue is technically challenging and dependent on collecting small amounts of tissue discarded from invasive surgeries. The generation of reproducible and scalable cardiomyocytes derived from IPSCs, combined with the use of NMR metabolomics to measure metabolic changes in response to disease will enable application to research studies investigating normal and abnormal cardiac development, screening of drug efficacy to replace large-scale use of animal models and the development of regenerative medicine and cell therapy protocols.

The continuing increase in the incidence of cardiac disease with rising economic and societal costs underpins a clinical need for understanding disease progression and developing new drugs and cell therapies. Induced pluripotent stem cells (IPSCs) have been reprogrammed from a somatic (terminally differentiated) cell to the pluripotent phenotype. They're able to self-renew and differentiate into multiple cell types. This project will use NMR metabolomics to determine the metabolic changes during cardiomyocyte dysfunction using IPSC-derived cardiomyocytes as an in vitro model.

In the project IPSCs will be differentiated to the cardiomyocyte lineage using combinations of cytokines and growth factors that mimic the embryonic development of cardiac tissue. The efficiency of cardiomyocyte differentiation will be determined by analysis of genes and proteins expressed by cardiogenic lineages. Metabolic regulation of IPSC-derived cardiomyocytes in response to drug treatment that induces a disease phenotype will be measured using NMR metabolomics. Training will be provided in the maintenance and differentiation of IPSCs, semi-quantitative and quantitative PCR, immunofluorescence, NMR metabolomics, bioinformatics and computer modelling.

Additional requirements: N/A