Dr. Michela Mazzon
University College London
MRC Laboratory for Molecular Cell Biology
Dr. Michela Mazzon is a Researcher in the Medical Research Council Laboratory for Molecular Cell Biology at the University College London.
Throughout her time working as a researcher at several universities both in Italy and the UK, Dr. Mazzon has worked on a large variety of DNA and RNA viruses and on several aspects of cell-pathogen interaction, including innate immunity, virus trafficking, and cell metabolism, with the final goal of applying this knowledge towards the development of novel anti-viral approaches.
In addition, to address the growing need for virology service providers both from industry and academia, in 2017, Dr. Mazzon founded Virology Research Services. Based at UCL, Virology Research Services combines state-of-the-art, high-throughput facilities with the knowledge and know-how of experienced virologists,offering expert support to scientists developing vaccines and antiviral agents.
Ahead of her presentation at ISNTD d³ 2018, the annual conference by the ISNTD on drug discovery and diagnostics, we catch up with Dr. Mazzon in this Infectious Thoughts interview and find out more about her current research as well as the ongoing gaps and challenges in the race to find novel vaccines and antivirals to control emerging and re-emerging viruses.
A number of viral diseases, including those on the Neglected Tropical Diseases list, have the potential to threaten very large parts of the population and even escalate into deadly epidemics or pandemics, particularly in resource poor settings. How is your current research looking to tackle this?
Indeed, recent outbreaks have helped raise awareness of the threats viruses can pose to human and animal health, anywhere in the world. This has resulted in new funding and investments in the field, including incentives to accelerate the discovery of new vaccines and antiviral agents. However, the development of vaccines or therapies against new viruses is often based on what has worked in the past, but for many challenging viruses novel, pathogen-specific, and knowledge-based approaches will be needed.
Our research focuses on the development of modern, high-throughput, and knowledge-based assays and solutions. For instance, recent data from the dengue vaccination program has shown that in vitro antibody-mediated virus neutralization does not correlate with protection and this is due to dengue-specific phenomena, such as antibody-dependent enhancement (ADE), as well as differences in epitope accessibility between wild-type and lab-adapted strains.
Equally, ADE remains an ill-defined mechanism that cannot be accurately recapitulated by the current in vitro assays. This calls for the development of new tools, including cellular systems, constructs, and virus-like particles (VLPs) that can better mimic the scenario in vivo.
Additionally, in collaboration with our colleagues at University College London (UCL), we are using high-throughput and high-content phenotypic screenings towards the development of host-targeted broad-spectrum antivirals. Our work to date has focused on the concept that compounds targeting those conserved cellular pathways exploited by viruses can block infection by all of the viruses using those same pathways. We are now starting a phenotypic screen of a large small-molecule compound set to identify candidates to take forward in our drug discovery program.
Our approach combines an active research program with the provision of virology research services, something we believe is much needed in the field of infectious diseases. The ultimate goal is to help overcome the obstacles associated with virus research, especially for neglected tropical viruses.
What are some of the main challenges, both in the lab as well as further down the line in the field, that you are faced with or trying to avoid?
The main challenge is probably the viruses themselves! They are many, varied, constantly emerging or re-emerging with subtle changes, and many have out smartened all of our attempts at controlling them. It’s almost as if the scientific community is continually forced back to square one.
Add to this the need for rapid progression from the identification of a new virus to delivering a vaccine or antiviral to the affected population, maintaining interest and funding, and verifying and integrating the information collected across multiple labs and scientific disciplines.
There are no simple solutions to these challenges. In our experience, cooperation among the scientific community and a sustained effort to support research and increase preparedness are good starting points.
Are there specific technologies, which you would like to see developed which would help accelerate your research?
There are many, so it’s a very exciting time to be in this field; in fact, we publish a weekly newsletter and blog that highlights important discoveries and technical advances. We are following two technologies in particular: artificial intelligence (AI) and 3D culture models.
AI and machine learning are exploding in many biomedical fields, but the impact they could have in virology and infectious disease research is still largely unexplored. Can AI help us collect, prioritize, validate, and extrapolate information from the vast amount of literature, field trials, and IP applications? Or how can we apply AI to phenotypic screens to identify new drug targets, or reveal new mechanisms of cell-virus interactions?
3D culture systems can help us fill the gap between cell lines and animal models of disease, that too often do not recapitulate viral pathogenesis. Also, one of the main hurdles in drug discovery is the pharmacokinetics and the in vivo toxicity of the candidate compounds, which can only be assessed in more physiological systems. 3D cultures could help assess some important properties and prevent a number of suboptimal compounds from reaching more expensive preclinical stages of drug discovery.
In 2017, you founded Virology Research Services, based at the University College London. What are you aiming to provide to fellow academics and colleagues in the industry?
At Virology Research Services, our mission is to support global research with the aim to tackle viral infectious diseases. We do this by permanently hosting the knowledge, know-how, and specialized facilities needed to advance anti-viral research, which we make available to both industry and academia. This approach to virology research is advantageous because it removes the need for each new project or laboratory to ‘reinvent the wheel’.
Also, the costs associated with establishing the specialized facilities and training can be prohibitive for smaller enterprises and less-well-funded institutes. UCL hosts the state-of-the-art facilities, the high-level containment, and in-depth expertise that are needed to face the R&D challenges of pathogen research. This collection of resources is invaluable for those seeking to outsource critical steps of their R&D pipeline to expert hands, including Pharma, research centers and academia, and virtual companies that want to test and develop disruptive ideas but do not have the facilities to do so. For example, our antiviral discovery services make use of the state-of-the-art equipment available to us through the UCL LMCB High-Content Laboratory, including the Perkin Elmer Opera Phenix High Content Screening System. Screens can be followed up by validation, determination of potency and toxicity, and mode of action studies.
We’re also helping industry with vaccine development by performing traditional neutralization and PRNT assays, as well as virus-specific assays, including ADE for dengue, HAI for influenza, and ELISA to determine immune response signatures. We also know that flexibility is often critical to the success of a project, which is why we often work with our clients and partners to develop bespoke assays and services.
Are there specific partners you would like to enter in collaboration with or even open a dialogue with?
We know that our services can greatly expedite the efforts of small and medium enterprises, especially those without established viral containment facilities and virus handling expertise, and we get a lot of satisfaction from these projects. Having said that, we certainly have the facilities and expertise suited to larger projects with established pharma companies involved in vaccine and drug discovery, and we welcome any opportunity for collaboration.
For more information please contact:
Dr. Michela Mazzon
University College London