Immunology, interactions and interplay

As we age, our bodies become more prone to infection and disease, and vaccination becomes less effective. Dr Martin Turner, Head of the Immunology programme, talks about why a deeper understanding of the immune system is key to lifelong health and why—after almost 30 years at the Institute—the programme’s research continues to excite.

Wrinkles and grey hair may be the most visible outward signs of passing years, but inwardly, a decline in adaptive immunity is one of the most significant hallmarks of ageing, making us more susceptible to infection and disease, and poorer at responding to vaccination.

As we get older, our immune system changes. It becomes less adept at fending off illness and infection and less able to promote tissue homeostasis and repair. This is why older people are more prone to flu and may also explain higher cancer rates among older people. But although we can see the impact of the ageing immune system, we need to know much more about how it works in order to improve it.

Today, Dr Martin Turner is Head of the Immunology programme. When he joined the Institute in 1997, the human genome had still to be sequenced, the Higgs Boson particle had yet to be discovered and Google did not exist, but his excitement for research endures.

“We are 25 years past sequencing the human genome. Some 20,000 protein encoding genes have been identified, a similar number to those in the nematode worm. That’s worth reflecting on, because humans are considerably more complex than C. elegans,” he says. “Very little is known about many of these 20,000 genes. What is even more challenging to understand is that each gene produces many distinct RNAs or alternative transcripts to form a transcriptome and these drive the complex behaviour of different cells in the body. You can think of the genome as a zip file for the transcriptome. What’s so exciting is that there’s still so much to discover.”

Over the next four years of the Institute’s immunology research, the focus is to discover more about the fundamental biology of our immune system, knowledge we need in order to improve vaccines, immunisation strategies and cell-based therapies. There are many questions still to answer, including how long-term immunological memory is generated and persists, and why, as we age, we become less resilient to respiratory infection.

Our immunological memory describes the way our immune system recognises and reacts to pathogens it has previously encountered, thanks to long-lived memory B and T cells created during the initial response which can persist for years and even decades. In their work in this area, the programme’s research teams want to understand the molecular mechanisms which regulate the formation of long-lived B cells which secrete antibodies and so-called CD8 memory T cells which can recognise cells infected with viruses or bacteria.

“This kind of immunological memory is very important, particularly in older people with diminished antibody responses, or in situations where viruses have undergone changes in their antigenic makeup so that they're no longer efficiently recognised by antibodies, and has significant practical applications,” says Turner.

Just like the complex interactions and interplay needed to shape an effective immune response, Turner is proud of the complementary expertise held by the research groups in the programme, dovetailing to advance key facets of the fundamental biology of the immune response: how different B and T cell types are produced and activated, B cell training in pathogen recognition, immune cell proteomics and how genes are switched on and off during these processes.

There are wider reasons why Turner believes the Institute is perfectly placed to answer these important questions, from the synergies between its Immunology, Signalling and Epigenetics programmes and the expertise of its technical staff, to its collaborations with biotech companies on the Babraham Research Campus and beyond.

“The Institute’s technical specialists are extraordinary. We absolutely rely on the expertise of the technical staff who support our use of mouse models to understand immune responses, and on the staff who are experts in the high-dimensional flow cytometry, sequencing and imaging technologies we use,” he says. “It’s impossible to overstate how important they are in delivering the world-class science we do here.”

Beyond generating new scientific knowledge in fundamental biology, Turner is also passionate about the development of researchers from the start of their careers onwards. Together, the Institute and Campus provide an innovative training environment for the next generation of researchers. Many studentships are shared between the Institute and Campus biotech firms, giving young researchers unrivalled experience in both fundamental research and the biotech industry. 

“We have trained—and continue to train—many students and postdocs who go on to successful careers elsewhere, either as research group leaders or in industry in start-ups and scale-ups as well as big pharma leaders like AstraZeneca and GSK,” Turner concludes. “Many of the young researchers joining the Institute now will be the future leaders in the field, in both academia and industry. Their success speaks volumes about the Institute’s reputation—this is a fantastic training environment—and the quality of the young people we are training.”