Announcing the eight Lister Research Prize Fellows 2022

Immune checkpoint therapies – antibodies directed against checkpoint proteins such as programmed cell death-1 receptor (PD-1) – benefit about 30% of cancer patients. But why do the majority of patients not respond?

Shoba’s aim is to determine whether early immune activation triggers driven by tumour cells can play a key role in enhancing response to checkpoint therapies. Her team discovered that early immune responses driven by Innate Lymphoid cells (ILCs) can be regulated by PD-1 in normal immune system. But whether PD-1 can singularly control early immune responses driven by ILCs in tumours remains unclear. Determining immune modifiers that drive robust early immune activation may be key to improving checkpoint therapies and stratifying patients.

Fungal pathogens are underappreciated causes of human disease and death. Elizabeth’s group studies how relationships between soil-dwelling fungi and bacteria influence disease.

They have shown that transient interaction with bacteria can cause changes in fungal stress resistance and resulting in increased virulence. In some cases, stable partnerships (endosymbiosis) between bacteria and fungi can help them evade the immune system’s defences. By investigating the molecular mechanisms by which fungal-bacterial partnerships influence pathogenesis in a variety of species, Elizabeth’s lab is identifying new ways to block fungal stress resistance and improve patient outcomes.

T follicular helper (Tfh) cells are a key immune cell population controlling the generation of high affinity germinal centre B cells and antibody responses. Key questions regarding how antigen density and receptor stimulation regulate Tfh cell development and maintenance remain unanswered.

David’s lab employs state-of-the-art tools to reveal how T cell receptor signal strength and duration impact upon Tfh cell formation and the ensuing development of antibody-secreting lymphocytes.

Better understanding these processes will help to design more effective vaccines and immunotherapies.

Double-strand breaks in DNA are extremely dangerous if not repaired, and can cause genomic instability, cell death and cancer.

Amanda’s lab studies a key mechanism to repair these breaks, called non-homologous end joining (NHEJ). They use cryo-electron microscopy and biochemical techniques to understand large multicomponent assemblies critical for DNA repair. Proteins involved in NHEJ are also important during viral infection, which they are also investigating.

Understanding these mechanisms has the potential to develop specific therapeutics against cancer and viruses.

James’ main interest lies in understanding how the genome encodes the information required to create complex organisms.

His lab specialises in understanding how DNA is structured within the nucleus and how this relates to gene expression.

They have developed new approaches that allow DNA structures to be determined at very high resolution. These are providing insights into the fundamental mechanisms by which genes are controlled as well as enabling them to understand the effects of sequence variation on human disease.

Marco’s group develops chemical tools to assess how DNA changes structurally and chemically during ageing and disease development. Specifically, they investigate the prevalence of non-helical DNA structures and DNA chemical modifications in the context of ageing related disorders.

They aim to develop chemical-based tools to perturb, in real time, DNA-methylation in ovarian cancer cells using light irradiation.

This technology will underpin druggable pathways to restore the sensitivity to therapies whilst also identifying diagnostic markers to monitor resistance acquisition.

Glaucoma is the commonest cause of irreparable blindness globally and poses numerous challenges. Detecting disease early is challenging, response to available treatments is variable, and it is impossible to predict which patients will become blind.

The solution to these challenges lies in the fundamental cause of glaucoma: its complex genetics.

Anthony’s team is identifying many new genetic markers of glaucoma and building prediction tools that will enable population screening for early detection and enable more personalised glaucoma care, saving sight and considerable cost.

Despite bacteria from the Streptomyces genus being the source of most clinically important antibiotics, scientists have only recently begun to explore the genomic and functional diversity of Streptomyces in our soils. A thorough exploitation of Streptomyces for the discovery and production of antibiotics will depend on a much better understanding of their genomic and functional diversity, and of the developmental and cellular mechanisms that enable this remarkable metabolic potential to be realised.

Streptomyces are peculiar in that they often contain giant linear plasmids, which are often involved in complex metabolic processes including antibiotic production. Tung’s group is interested in understanding the fundamental mechanisms by which these important linear plasmids are faithfully segregated and how they might contribute to the genome evolution in antibiotic-producing Streptomyces.