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Attacking tuberculosis bacteria: an interview with Mónica Varela

This summer postdoctoral researcher Mónica Varela from the Institute of Biology Leiden was awarded a Veni grant from the Dutch Research Council (NWO). Six questions about her project and hopes for the future.

Congratulations with your Veni grant! What was your first reaction when you received the news?

‘It was actually kind of funny. It was about 8.00 in the morning and there was nobody around in the lab. So I started calling people to tell them about the good news.’

What does it mean for you to be honoured with a Veni grant?

‘To receive this grant means a lot to me. It is a prestigious grant, and to receive one was just the right thing at the right time. I had just finished my previous EU-funded research and now I can follow it up by “conquering the tuberculosis fortress” as I call it.’

Mycobacteria (green) hide in compact cell aggregates (granulomas). Photo by M. Varela.

What is this ‘tuberculosis fortress’?

‘The bacteria that cause tuberculosis hide in aggregates of immune cells forming like a fortress. I think this structure, called granuloma, actually helps the bacteria: it limits the effectiveness of immune responses and antibiotics. We want to avoid the formation of granulomas or reduce its size. In my previous research we identified the mechanism involved in the formation of granulomas, so now we will apply that knowledge and focus on finding drugs that can potentially be used in clinics.’ 

How big is the problem of tuberculosis?

‘According to the World Health Organization, tuberculosis is one of the top 10 killers worldwide. Treatment nowadays consists of a combination of antibiotics used for a long period of time. This leads to low treatment compliance and an increase in antibiotic resistant bacteria. At some point it will be difficult to treat tuberculosis if we keep doing it in the same way we are doing it now. So alternative ways of treatment are urgently needed.’

If antibiotics are not the answer, then what treatment are you looking for?

‘Our approach is twofold in order to be more effective. The first path we are investigating is by blocking a particular inflammatory pathway involved in the progression of the disease. We are looking for drugs that are able to do that in our zebrafish tuberculosis model. That could be a known drug that we then can reuse for this purpose. The second path that we are taking is bacteriophage-based therapy. That means that we will use a virus that is harmless to people but kills the tuberculosis bacteria and can help to keep the infection under control.’

The grant is for three years; where do you hope to be in three years’ time?

‘I hope this will lead to a new grant (laughs). This research will definitely generate good data for follow up research. Three years is not enough time to find a cure for tuberculosis; implementing a new treatment takes 10, 15, maybe 20 years. But we need good data on animal models like zebrafish to start with before clinical trials in humans can take place.’

Header image: Zebrafish larva infected with Mycobacteria (in magenta). Photo by M. Varela.

A total of 25 young researchers at Leiden have received a Veni grant in 2019. Each year, the Dutch Research Council (NWO) awards Veni subsidies to excellent researchers who have recently obtained their doctorate. Successful applicants receive a maximum of €250,000 to carry out research inspired by their curiosity. In combination with Vidi and Vici, the Veni forms part of NWO’s Innovational Research Incentives Scheme.

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