GOING GLOBAL

From making discoveries about chronic lung disorders to managing a research programme to improve health around the world, Dr Sarah Puddicombe has taken her career from lab to office – and beyond.

Joining the University of Southampton in the early ‘90s, Sarah was part of a team of scientists who discovered ground-breaking potential for interferon beta, paving the way for pioneering COVID-19 treatment.

Interferon beta is a naturally occurring medication in a class called ‘immunomodulators’. The team found a defective interferon beta response to virus infections in the airways of those with chronic respiratory disorders. This novel discovery indicated a use for interferon beta to help protect airways against viral infections – and it is now being used to help improve the outcomes of COVID patients.

Today, Sarah is Assistant Director of Global Health based within the University’s largest enterprise unit, NETSCC (the National Institute of Health and Care Research (NIHR) Evaluation, Trials and Studies Coordinating Centre), based at the University of Southampton Science Park.

Sarah arrived in Southampton in 1992 as a research assistant and also studied part-time for her PhD.

“My PhD was focused on epidermal growth factors and their receptors whose signalling can go wrong and drive uncontrolled cell growth, leading to breast cancer,” she explained. “I made modified versions of these growth factors to find agents to alter this signalling and to help prevent cancer.”

Following her PhD, she worked with Professor Donna Davies and Professor Sir Stephen Holgate, initially looking at these growth factors and signalling pathways in the repair of asthmatic airways in responses to different environmental insults.

Her research involved taking cells from airways and growing these at an air-liquid interface. “I was able to grow miniature models of the airways to replicate the lung lining – layers of cells with specialised mucus producing cells, and cells with beating cilia which help clear mucus and irritants from the airways,” she said. ‘’My work using these models and biopsies compared healthy and diseased airways’ responses to external insults and looked at factors involved in the underlying disease changes observed in the airways.”

It was around this point that the team discovered a weakness in the protective barrier of the airway to various insults in asthma. They also found impaired antiviral responses to respiratory infections and identified the potentially game-changing influence of interferon beta, capable of improving antiviral responses.

“Levels of interferon beta produced in asthma and in Chronic Obstructive Pulmonary Disease, or COPD, were lower in response to virus infections and, by adding interferon beta back in, you could help protect the airways from these viral infections,” explained Sarah.

In 2003, capitalising on the opportunity to use models of airways disease to identify other protective agents – in addition to interferon beta – able to improve the barrier function chronic airways diseases, Synairgen was spun out by Donna, Stephen and Professor Ratko Djukanovic. Sarah set up the early discovery programme.

She said: “In the early days of Synairgen, we were looking at the integrity of the intercellular connections. We found there were specific weaknesses in some of those connections in asthma. This was making the epithelium [airway tissue] susceptible to triggers such as air pollution, cigarette smoke and dust mite allergen agents. This defective airways barrier appeared to contribute to the increased susceptibility to disease exacerbations in response to environmental agents.

“We wanted to work out what could reverse that, and found that certain growth factors improved the integrity of the intercellular connections and restored barrier function. In parallel, interferon beta became a lead candidate given its ability to restore asthmatic airway responses to viral infections. This resulted in various studies in patients with asthma and COPD using interferon beta delivered by a specialist inhaler.”

When COVID hit in late 2019, interferon beta was an obvious candidate. “The minute I heard about COVID, I thought that interferon beta may really help COVID patients with existing airways disease,” said Sarah. “I am proud to have had a part in the early discovery work and have followed Synairgen’s progress over the years with its studies. It is so brilliant to learn of the latest trials helping to treat COVID patients.”

In 2008, Sarah left Synairgen to join NETSCC to manage NIHR research programmes providing evidence to inform policy and practice in the NHS, public health and social care.

“I was keen to apply my research knowledge to another side of research, this time as a research funder – identifying priorities for NIHR applied health research and funding calls, and helping to stimulate the research community to respond to these needs,” she said.

Most recently, Sarah has set up NIHR Global Health Research programme awards, using UK Aid funding to support research and training partnerships in developing countries to address major health challenges. The portfolio now includes 100 awards with partnerships in over 50 developing countries.

She said: “These partnerships are identifying and tackling major research gaps and endemic issues that disproportionately affect the health burden on those living in developing contexts.”

Projects include improving anti-venom treatments for snake bites in Africa; avoiding preventable deaths through better treatment of chronic respiratory diseases; preventing injuries and improving trauma care in Nepal; and developing global genomic surveillance for antimicrobial resistance.

“In February 2020, I visited teams based in South Africa,” added Sarah. “It was a privilege to visit the research sites and meet the local communities and teams who are directly benefitting from these research activities, and to understand the positive impact of research and training towards improving health outcomes in these developing contexts.”

Find out more nihr.ac.uk/explore-nihr/fundingprogrammes/global-health.htm