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From clinic to lab: making the switch to fight TB

1 March 2016

It has been a busy few weeks for Dr Laura Gleeson, with a paper published in the Journal of Immunity which could change the direction of TB research worldwide.

Claire O'Connell caught up with her recently.

TB is a devastating disease, and it could get worse. As the bacterial strains that cause the illness become resistant to treatments, the search is on for new therapies that can boost our defences against the hardy bugs, and Dr Laura Gleeson is on the case.

A medical doctor by training, Laura fell into lab research almost by accident. After studying medicine at Trinity College Dublin and doing basic hospital training, she needed to decide on her specialist area, but wasn’t yet sure what to do.

‘I decided to take a year where I would have a think about it, and I took a job as a clinical lecturer with Trinity School of Medicine at St James’s Hospital,’ she explains. ‘Through the lecturing I got involved in the research in Professor Joe Keane’s lab almost by accident, but I really liked it’.

TB defences

That fortunate connection led to Laura starting a PhD with Professor Keane, a HRB Clinician Scientist. Her project, which is funded through a HRB Health Professional Fellowship plugs into a common theme of interest in the Keane lab: to figure out how our immune systems naturally respond to and clear the bacteria that cause TB, so that we can develop new therapies to strengthen those defences.

She knew that immune cells called macrophages sometimes change the way they make energy and undergo a ‘glycolytic shift’ when there is an infection to be tackled, and she wanted to find out if this the case in TB too.

This is where the help of patients undergoing bronchial procedures at St James’s was invaluable: they willingly donated non-TB-infected macrophages from ‘washings’ of their lungs to be used in the study.

‘Patients are usually extremely helpful, we couldn’t do it without them,’ says Laura. She grew the lung macrophages in the lab and infected some with the bug Mycobacterium tuberculosis, which causes TB. ‘We saw that infected macrophages did switch to this glycolytic state,’ she explains. ‘So we changed the conditions they were growing in to prevent this switch from happening, in order to find out how important glycolysis was for fighting TB. And when we did this, we found that glycolysis is needed to make important molecules to fight the bacterium, including interleukin 1B, and ultimately clearing the bugs out of the cells’.

The findings were published earlier this month in the Journal of Immunology. Now that we know frontline immune cells in the lung can perform better against the TB bugs in this state of glycolysis, the next step is to find medicines that can enhance this switch in human patients.

‘We are looking to see if there are drugs already out there that are safe and affordable and can ramp up this glycolytic shift in response to TB to be able to enhance clearance of the bug,’ explains Laura. ‘It will need a lot more research to see if it works in humans, but it could open the way for new treatments’.

Changing environments

Switching between hospital work and lab research has made Laura realise how different the two environments are. ‘I worked for three years in a hospital, where as a junior doctor you have a list of urgent jobs every morning, but in the lab you need to get used to self-direction. Also, because TB grows so slowly sometimes you don’t get results for weeks, so you have to have the mindset and planning to deal with that’.

Laura currently mixes her lab work with teaching in Trinity and doing on-call sessions in St James’s and she loves the variety in her work and meeting new people to work with. 

‘On a given day, I could be working in the lab in James’s Hospital, discussing ideas with colleagues in the Trinity Biomedical Sciences Institute, taking samples in the bronchoscopy suite, or seeing patients in the TB clinic. I also get opportunities to travel to conferences, meeting some amazing scientists and clinicians involved in research. I love that, the opportunities for collaborating with people’.

Curiosity-led future

Now finishing up her PhD with Prof Joe Keane, Laura is preparing to finish her training as a specialist in respiratory medicine, which will mean going back into the clinic.

‘I am looking forward to that, I do miss it a bit,’ she says. ‘In the longer term I would really like to work partly in clinical and partly in research. The research gives you a goal to work towards, and it is really cool to come up with questions and be able to investigate them yourself’.

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