Dr Sergi Padilla-Parra uses advanced light microscopy techniques to study the entry mechanisms of enveloped viruses. This approach is based on quantitative fluorescence microscopy and shows how different viruses enter the cell and how different endocytic pathways are regulated in the presence or absence of pathogens.
Novel light microscopy techniques allow us to track single viruses. From a virus centric approach, we can now study interactions between the host and the virus. In the case of HIV, we could demonstrate that the virus might enter the cell through endocytosis. A better understanding of virus-cell interactions will ultimately help us test and develop new drugs and vaccines.
Ultimately, medical research must translate into improved treatments for patients. At the Nuffield Department of Medicine, our researchers collaborate to develop better health care, improved quality of life, and enhanced preventative measures for all patients. Our findings in the laboratory are translated into changes in clinical practice, from bench to bedside.
Sergi Padilla-Para: The majority of viruses enter the cell through a mechanism called endocytosis. This mechanism allows the cell to internalise nutrients, big proteins, or to control the concentration of receptors in the membrane. The virus highjacks this mechanism to gain entry to the cell; it is then transported into vesicular trafficking and eventually fuses. My lab studies these processes with the use of advanced light microscopy.
Q: How can we block these entrance mechanisms?
SP: The important thing is to understand quantitatively the processes that the viruses use to get inside the cell. We go from a virus centric approach to the interplay between the host and the virus. Our lab is studying HIV1, among other viruses. This is a nice example of how the virus triggers some cell mechanisms in order to internalise and eventually fuse. For a long time it has been understood that the virus fuses into the plasma membrane, but the new techniques based on light microscopy that we are developing in my lab, have helped to show that the virus might be getting inside through endocytosis. A better understanding of these processes will undoubtedly help to develop drugs, small molecules or peptides that will keep the virus at bay.
Q: How can we improve antiviral drugs?
SP: We need to apply these new methods and gain a better understanding of how the virus is triggering some key enzymatic players. The idea is to follow single events but to also understand at the same time how these cellular factors are being used by the virus to get inside the cell. If we can actually determine the abnormal activities of these factors then we can develop novel strategies, novel targets for drugs to be more effective.
Q: What are the most important lines of research that have developed in the past five or ten years?
SP: An important line of research that has developed is the application of novel light microscopy techniques, like real time single virus tracking. This was applied to HIV entry and it was discovered that HIV might enter the cell through endocytosis.
Q: Why does your line of research matter and why should we put money into it?
SP: There are two lines of research that are really important. One is the virus centric approach and techniques that allow, for instance, to study a structure using electron microscopy (EM), cryo-EM. The other line of research is based on developing vaccines and studying how the immunological system reacts to HIV infection. Our research fits very well and fills the gap between these two lines of research. We have accessibility to single events and we can now follow single viruses and understand how, when and under which conditions this fusion occurs, so I think this is worth investing in.
Q: How does your research fit into translational medicine within the Department?
SP: There are two different lines of research that are quite translational. Firstly, we check events at single virus or single cell level, and apply that to high content imaging. The development of new techniques in high content imaging will help to screen new drugs to block virus entry. Secondly, it is focusing on the factors that allow the HIV1 virus to enter the cell. Then we can point at these targets then we can develop new drugs, new peptides, and new vaccines to block the virus before the process of entry in to the cell.