Department of Clinical Medicine
Supervisor: Dr Aideen Long
PKC isotype expression and localisation within hepatocytes
Hepatitis C affects nearly 200 million people – that’s 3% of the world’s population. It’s the major cause of liver damage and can lead to liver cancer. At the moment, Interferon-Alpha is the current treatment for Hepatitis C. However, it has poor response rates; it’s expensive and can lead to undesirable side-effects, such as depression.
In the Institute of Molecular Medicine in Trinity College, we aim to investigate how Interferon-Alpha works and by doing this we hope to develop better strategies in the fight against Hepatitis C.
My supervisor, Dr Aideen Long, explains how the idea for this research came about: “I was reading a paper showing that the clearance of Hepatitis C in response to Interferon required the enzyme Protein Kinase C (PKC). From previous work, I knew that the virus could manipulate PKC and stop it from working (signalling). So I hypothesized that in hepatocytes the virus would manipulate PKC and prevent the cells from responding to Interferon therapy. I spoke with Professor Cliona O’Farrelly about that and we applied for and received funding to study mechanisms of Interferon-Alpha resistance in the Hepatitis C virus.”
We use wet blotting to identify which PKCs are present in hepatocytes and microscopy to visualize their locations. We did this before and after Interferon treatment to see if there were changes in the advancement or location. We also used a range of methods to block PKC activity and found that some PKCs were required for Interferon for signalling while others were not.
Our work has shown which PKCs were involved in Interferon-Alpha signalling. At the moment we’re examining if the Hepatitis C virus can disrupt PKCs and thereby evade Interferon-Alpha response. We hope that this will give us more insights and new strategies in how to combat Hepatitis C.