Meet The Expert: Tim McHugh

Professor Tim McHugh is Professor of Medical Microbiology and Director of the Centre for Clinical Microbiology (CCM) in the Division of Infection and Immunity, Faculty of Medical Sciences. Tim is also Graduate Tutor (Taught) for the Faculty of Medical Sciences. 

Tim’s research at the CCM focuses on the improved diagnosis and treatment of microbial infections with particular reference to antimicrobials and the evolution of antimicrobial resistance.  CCM has an emphasis on respiratory infection with studies on tuberculosis as well as the microbiome and resistome in patients with chronic lung disease. Working with drug-resistant tuberculosis has meant that a key element of this work is supporting the development of appropriate laboratory facilities for the handling of high consequence pathogens, recently leading to a role for the Centre in the COVID-19 response.

Tuberculosis remains a global health emergency and with projects that cover the spectrum of science from transcriptomic analysis of bacterial responses to antibiotic treatment through to clinical and operational research in hard to reach communities, the Centre contributes at each end of the anti-tuberculosis drug development pipeline - at one end screening novel compounds for activity and exploring the mechanism of action, whilst at the other end of the pipeline providing expertise and infrastructure for the delivery of TB treatment trials. An underlying theme is the development of biomarkers of treatment outcome, whether transcriptomic analysis of in vitro treatments for drug development or the more complex picture of monitoring success of treatment in patients.

Another important element of CCM’s work is capacity development.  The team provides training for laboratory scientists, both on-site in London or global partners, through participation in networks such as PanACEA and PANDORA-ID-NET, to enhance skills in microbiology laboratories.

We caught up with Professor Tim McHugh to understand what motivates his research and how he navigated carrying on his important research during the pandemic.

 We asked Tim ten questions, and this is what he told us…

Question 1: What inspired you early on in your career to specialise in microbiology?

Tim: At school and subsequently during my degree, I became fascinated with parasitic worms, how they interacted with their hosts, their complex life cycles and, importantly, how they impacted the communities where they were endemic. My PhD was on the parasitic nematode worm, strongloides and then I did postdocs studying the parasitic protozoa, giardia and toxoplasma. My pathogens have got smaller and whilst working at St Georges I began to apply my knowledge of intracellular pathogens to the study of leprosy and tuberculosis, moving from eukaryotes to prokaroytes, but that complex interaction between a microorganism and health of its host was still the focus and drives my work now.

Question 2:  Can you explain what is so remarkable about the work undertaken at the Centre for Clinical Microbiology?

Tim:  We provide expertise in TB microbiology for global clinical trials. Although many laboratories can ‘do’ TB microbiology, we have unique expertise that is recognised internationally. We have a framework of working that starts from site recruitment, through study delivery and ends with analysis and interpretation of the data. The hands-on microbiological expertise of our team is the platform on which this is built. This rigorous approach to clinical studies has enabled us to undertake a detailed analysis of the transcriptome of TB in patients undergoing TB treatment and, looking beyond TB, to develop approaches to explore the lung microbiome in patients with chronic lung disease.

Question 3: What is it about respiratory infections in particular that is so significant to make them an area in need of particular focus?

Tim:  I think the COVID-19 pandemic answers this question! It’s all about transmission and that first interaction between a pathogen and a ciliate mucosal surface. For TB we are focused on dissecting the physiological state of the mycobacteria in the lung with the aim of identifying the most effective drug treatments. Understanding the lung as an environment is critical. Some while ago we demonstrated the importance of a novel mycoplasma in patients with primary immunodeficiency, now with new tools, we are describing the whole microbiome in various patient groups and working out what conditions lead to poor outcomes for the patients.

Question 4.  Can you explain your work on the tuberculosis treatment trials and what is so remarkable about their results for patient outcomes?

Tim:    Mycobactrium tuberculosis is a tricky organism to work with. It has unique physiology and grows extremely slowly (the generation time for E. coli is 20 minutes, for M. tuberculosis it is 24 h), and of course we need to work in containment facilities (Containment Level 3 laboratories). With this in mind, we have two roles in phase II and phase III clinical trials. Some of the microbiology needs to be undertaken locally (we have sites across the world), and so we have created a framework that provides training, support and oversight of the work to ensure that every patient sample is processed correctly and that no data point is missed. Members of the team travel around the sites to supervise this activity. Our second role is in the specialist microbiology associated with novel drugs, providing the data on evolution of drug resistance and the mechanisms by which it arises in the clinical setting. We are very proud that the new antituberculosis drug, Pretomanid, was approved as part of a new multidrug resistant TB regimen by the FDA last year.  This is the first new regimen for MDR-TB approved and our data was fundamental to that approval.

Question 5:  How have you and your laboratory team managed to carry on your research during the lockdown?

Tim:   At lockdown we were busy supporting our TB clinical trials, studying AMR in gram negative bacteria and initiating a project on improved Lassa Fever detection, amongst other things. This all had to stop. However, we had the only Containment facility at the Royal Free suitable for COVID-19 work and so the Royal Free Infectious Diseases team approach us for support in processing patient samples for the various clinical studies and drug trials that were initiated for COVID-19 patients. I am very proud of the response of the team who, without hesitation, switched to this activity, learning new skills, putting in place the necessary safety structures and then putting in long hours doing fairly routine work. Those who were not able to travel into the laboratory were equally important, providing support and advice and backfilling online roles to release those able to come to the laboratory. It also gave me the opportunity to drive across lockdown London at 2am – a unique experience.

Question 6: Can you tell us more about your COVID-19 research – its objectives and what you hope will be the results?

Tim:  CCM is essentially a bacteriology unit, but our expertise in handling high consequence respiratory pathogens meant that we were well-positioned to support  COVID-19 studies. We worked with colleagues in Infection & Immunity to make sure that facilities across UCL met regulatory requirements and were made available to priority projects. Whilst I&I colleagues (who are real virologists) are leading some important discovery science, we at CCM have initiated projects building on collaborations that preceded COVID-19. For example, we have been using a hollow fibre infection system to model the pharmacology of anti-infective agents for TB and Gram-negative bacteria, but now, in a project led by Judy Breuer (ICH), are repurposing this approach to model the effect of novel antivirals on SARS-CoV-2. Similarly, building on previous collaborations with Chris O’Callaghan (ICH) and Claire Smith (ICH) in which we have been exploring the interaction of respiratory pathogens with ciliated lung epithelia, we are applying these techniques to SARS-CoV-2. These approaches and other studies in the pipeline are designed to help us understand the factors that drive COVID-19 pathogenesis and evaluate the most effective treatments for this infection.

Question 7:  Can you explain what your role as Graduate Tutor entails?

Tim:  The role of the Faculty Graduate Tutor (FGT) role is to ensure that our students have the full benefit of their time at UCL. I am primarily responsible for Taught programme students, working closely with my colleague Jill Norman who leads on Research students. I have oversight of all aspects of postgraduate programme development and delivery, supporting Divisions as they put together their new programmes and respond to change as the programmes develop, advising on curriculum design and delivery as well as navigating the regulatory requirements. The flip side of this is student support; any postgraduate student in the Faculty can bring their concerns to me for advice or, if necessary, for intervention.

Question 8:  How has the pandemic impacted students’ masters' programmes?

Tim:  When the decision was made to suspend face to face examinations, working with Blathnaid Mahoney (Faculty Tutor) and Jill Norman, we reviewed and approved the proposed changes to assessment for every module delivered by the Faculty of Medical Sciences (FMS). Using our knowledge of the programmes, we worked to ensure that students were treated fairly and that standards were maintained. When UCL went to remote working, our masters' students were just entering their projects and, in some cases, substantial periods of clinical experience. Naturally, they were concerned about how they would gain this experience - the reason they came to UCL. As FGT, I worked with student representatives and Division education leads to mitigate as far as possible the effects of the pandemic on their programmes, ensuring that the students not only achieved their masters' degrees but had the full benefit of being part of FMS.

Question 9:  What do you most enjoy about teaching FMS students?

Tim: I teach across a range of FMS programmes and I particularly enjoy those courses where the students have selected to study infection; I run an undergraduate SSC in the MBBS and an MSc module on exotic and emerging infections, these are always fun but were particularly relevant this year! Of course, I really enjoy project supervision – bringing students into our team, showing them how to design and perform experiments, demonstrating the importance of robust science and watching them develop as professional scientists. There is nothing more satisfying than meeting former students as their careers develop, finding that they are working in infection and that their progress is anchored in the time in our Centre.

Question 10: What’s the drive that makes you leap out of bed every day..?!

Tim:  This question made my family laugh! I am afraid I am not a leap out of bed person, more a night owl. What drives me? It is the challenge that infectious diseases pose for us; as we have seen with the COVID-19 pandemic, we need knowledge and expertise across a range of disciplines to meet that challenge. In any one day I may have detailed discussions about the genes up regulated in response to drug treatment in tuberculosis, and then in another project be considering the role of PPE in transmission of bacteria in ITU. I enjoy the satisfaction from application of the knowledge particularly in a team environment – but we also need to share our expertise.  Supporting students and colleagues to learn and develop is part of my DNA - whether it is our students and early careers colleagues, NHS professionals or the wider global community we work with through our collaborations.

Discover more here:

Professor Tim McHugh profile
Centre for Clinical Microbiology 
Biosafety Design Initiative
PanACEA
PANDORA-ID-NET
Pretomanid