Wellcome Trust PhD Student Cohort 2017
Academic work and experience prior to September 2017: I obtained my bachelor's degree in Biomedical Science at the University of Sheffield where I also completed a project at the Centre for Stem Cell Biology during a Wellcome Trust funded placement. Following my degree I worked for Axol Bioscience, a biotech start-up specialising in iPSC culture and differentiation, and Charles River, a contract research organisation which provides many services for the development of pharmaceuticals.
PhD Programme- Year 1- MRes and Project Rotations: During the first year of the programme I explored transplantation research in the context of three different tissues, in labs which ranged from basic science to more clinical research; (1) Assessing the expression of pro-survival growth factors by cardiac stem cells after transplantation into mice with myocardial infarction with Dr Georgina Ellison. Here I had the opportunity to collaborate with the Francis Crick Institute using laser capture microdissection. (2) Investigating the transfer of mitochondrial from mesenchymal stromal cells (MSC) to pancreatic islets prior to islet transplantation with Professor Peter Jones. (3) Investigating which MSC would provide the best support to primary human hepatocytes with the aim of improving hepatocyte transplantation with Dr Anil Dhawan and Dr Celine Filipi. This group is much closer to the clinic, with several clinical trials in process, and gave me excellent insight into how research is translated. My competency as a researcher has improved significantly thanks to the combination of reports, presentations and workshops during year 1 and the planning and direction of my final project has greatly benefited from being exposed to different researchers in similar fields, each with their own way of approaching challenges.
PhD Programme- Years 2 to 4- Doctoral Studies: For my thesis project I have chosen to join the department of diabetes with Professor Peter Jones. The replacement of β-cells through the transplantation of isolated pancreatic islets is a promising treatment for type 1 diabetes. However, this therapy has been limited by the progressive decline in islet function and viability during isolation and post-transplantation. Co-culture of islets with MSCs prior to transplantation can improve islet function and transplantation outcomes. This project will take two distinct approaches to elucidate mechanisms of MSC-mediated support of islets. The first will identify differentially expressed genes in MSC co-cultured islets. Through gene knockdown and overexpression, we will determine if genes of interest are biologically relevant to islet function. The second approach will focus on a mechanism known as mitochondrial transfer. Our pilot study revealed that MSC-derived mitochondria can be found within the outer cells of islets following co-culture. We aim to confirm and quantify transfer and determine if it is functionally beneficial to islets. Together, these investigations will support the development of an MSC-free culture approach where secreted factors, pharmacological pathway simulators and other biological components (i.e. isolated mitochondria) can be applied directly to islets in culture without the need for heterogenous MSC populations.
Ella Hubber ORCID webpage