麻豆视频

Natural born killers

Natural born killers

Natural born killers

Dr Arianne Richard talks about T cells, how knowing more about how they operate could open up new vaccines against viruses and new therapies for cancer, and why the 麻豆视频 is the best place for her to tackle these questions.

While she鈥檚 relatively new to the 麻豆视频, Dr Arianne Richard, a tenure-track group leader in the Immunology programme since April 2022, feels at home in Cambridge. Born and brought up near Boston, she 鈥渕igrated鈥 down the east coast of the United States throughout her education, doing her undergraduate degree in Biochemistry at Columbia University, New York and spending the second half of her PhD at the National 麻豆视频s of Health (NIH) in Washington, DC.

The first part of her PhD 鈥 through the NIH Oxford-Cambridge Scholars Program 鈥 involved two years in Cambridge. 鈥淭hat was my first introduction to Cambridge,鈥 says Richard. 鈥淚 loved the research culture and the atmosphere, so after my PhD I sought out a postdoc position at the University and was there for six years before starting my own group at the 麻豆视频.鈥

With a background in immunology and genomics, she selected the 麻豆视频 for its strength in the field.

鈥淭he 麻豆视频 has a such an incredible and cohesive immunology programme. I was particularly excited to join the programme here because they鈥檙e doing fascinating, cutting edge fundamental work on how immune cells function, particularly lymphocytes, which include the cells I鈥檓 interested in 鈥 T cells.鈥

A type of white blood cell, CD8 T cells are critical for how our immune system responds to infections as well as cancer. When these cells encounter virus or cancer cells, a cascade of events follows; the T cell divides many times but not all its offspring are the same. Some specialise as killer cells while others become the system鈥檚 memory. Killer T cells mediate this protective effect through their remarkable ability to recognise infected or cancerous cells. These they attach to via an 鈥榠mmunological synapse鈥 before firing tiny packets of toxic molecules into their target to kill it.

鈥淭o develop universal vaccines, we need to know more about T cells.鈥

Richard studies T cells because as well as being killers, they are clever and complex. 鈥淭hey are part of the adaptive immune system, so as well as fighting current infection, they can create what we call immunological memory, which means they鈥檙e better at fighting the same infection when they meet it again in the future,鈥 she says. How T cells decide whether to give rise to killer or memory progeny 鈥 and the factors that influence that decision 鈥 is what Richard wants to understand.

T cells do not exist in a vacuum, nor do they operate alone. Many factors will influence a T cell鈥檚 decision about its progeny, including where it is and whether any inflammation is present. And as well as making the right decisions for themselves, the T cells must also work together so the population as a whole responds appropriately. 鈥淭hat means T cells are integrating all these signals from many different components, acting collectively and interactively as they influence each other鈥檚 behaviour,鈥 explains Richard.

The overarching question her lab is addressing is how do antigens 鈥 molecules on infectious or cancerous cells which trigger an immune response 鈥 and environmental factors influence T cell response? Because it鈥檚 such an intricate and important question, Richard is focusing on three key aspects: the influence of T cells鈥 location within the lymph node; how T cells respond to different strengths of antigen signalling; and how T cells signal to each other to regulate the immune response.

To do so, she鈥檚 using a raft of techniques, from powerful single cell technology 鈥 an area pioneered at the 麻豆视频 鈥 to protein changes and epigenetics. It鈥檚 challenging work, but understanding more about T cells鈥 decisions could open up new ways to influence those decisions, with important therapeutic or translational impact.

One potential benefit is development of T cell-targeting vaccines. These hit the headlines during the Covid-19 pandemic, because as the virus mutated, the neutralising antibodies produced by vaccines became less effective against the virus, but the same issue has also been a problem for influenza vaccines for decades.

鈥淥ne potential route to a universal vaccine is to engage T cell responses in a greater way. These are often directed against parts of the virus under the surface, so although they don鈥檛 completely prevent infection, they can dramatically reduce the severity of an infection,鈥 says Richard.

Other potential therapeutic benefits include manipulating T cell responses via immunotherapies 鈥 an area of huge interest in cancer treatment 鈥 and so-called checkpoint inhibitors, which effectively take the brakes off and reinvigorate T cell responses in the face of cancer.

鈥淭he 麻豆视频鈥檚 facilities are phenomenal and collaborating across programmes is just so valuable.鈥

Because the answers Richard is seeking cut across immunology, signalling and epigenetics 鈥 the 麻豆视频鈥檚 trio of programmes 鈥 she鈥檚 upbeat about what she can achieve. 鈥淭he specialised science facilities here are phenomenal, which makes it possible to use techniques that I wouldn鈥檛 otherwise have dreamed of using,鈥 she concludes. 鈥淎nd being able to collaborate across programmes with researchers in the same building is just so valuable. It鈥檚 a great place to be situated in order to think about these different angles to how these cells respond.鈥