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Signalling

Signalling

Defining how cellular signalling pathways act together to coordinate cellular responses and how signalling mechanisms are affected by age.

Ultimately the cell is the basic unit of our health; when it functions well our tissues and organs are normal, but stress or damage can lead to loss of cell function, which may promote ageing and even pathology.  

The functioning of our cells is governed by a range of biochemical signalling pathways. By responding to information from the external environment, these pathways act together to coordinate the cellular response to stress or damage.

Our scientists are world leaders in the study of these signalling pathways, how they are regulated, how they control the viability of cells, tissues and organs and how this contributes to ageing and age-related chronic illness and disease.

By advancing our understanding of the cellular mechanisms that sense and adapt to different types of stress throughout the life course, our work will create new opportunities for therapeutic intervention to mitigate age-related physiological decline.

Aim 1: A new understanding of the cellular responses to stress and how this changes across the life course
The first stage of the programme will work to uncover the dynamic cell signalling processes involved in protein production, maintenance and degradation (proteostasis), and response to cellular stress, including the dysregulation of oxidant-sensing pathways. These are all drivers of age-related functional decline and chronic disease. Collaborating across our Epigenetics and Immunology research programmes, this work will focus especially on elements of the proteostasis network that govern the accumulation and removal of toxic aggregating proteins.

Aim 2: Identifying new strategies to sustain the health of ageing cells, tissues and organisms
Building on the work undertaken in aim 1, our second aim will explore how this new understanding can be applied to improve cellular responses to age-related stress. This will include investigating how autophagy can be harnessed to improve protein clearance, whether restoring lysosome function can reverse age-associated changes, and whether components of the integrated stress response signalling network can be targeted to promote healthy ageing. Our programme of work will integrate experiments across a diverse collection of model cells and organisms (yeast, worms, flies, mice, human neuronal cells) to study the ageing process.

Aim 1: A new understanding of the cellular responses to stress and how this changes across the life course

Explaining the breakdown in proteostasis across the life course

Understanding changes to the PI3K signalling network during ageing

The role of reactive oxygen species and protein kinases/phosphatases in sensing and maintaining epithelial barrier function

Aim 2: Identifying new strategies to sustain the health of ageing cells, tissues and organisms

Boosting autophagy to improve proteostasis

Enhancing cell recycling mechanisms to mitigate stress

Enhancing the integrated stress response to promote stress resilience, lifespan and health span

Azzi C, Rayon T 21 Apr 2024, PMID: 38648722 Current opinion in genetics & development

Superti-Furga G, Agostinho M, Bury J, Cook S, Durinx C, Ender A, van Luenen H, Lund AH, Medema RH, Miączyńska M, Nickel D, Pelicci PG, Puisieux A, Ripatti S, Sander M, Schubeler D, Serrano L, Sommer T, Sonne-Hansen K, Tomančák P, Vives J, Vontas J, Bettencourt-Dias M Apr 2024, PMID: 38514456 FEBS letters

Chen X, Tsvetkov AS, Shen HM, Isidoro C, Ktistakis NT, Linkermann A, Koopman WJH, Simon HU, Galluzzi L, Luo S, Xu D, Gu W, Peulen O, Cai Q, Rubinsztein DC, Chi JT, Zhang DD, Li C, Toyokuni S, Liu J, Roh JL, Dai E, Juhasz G, Liu W, Zhang J, Yang M, Liu J, Zhu LQ, Zou W, Piacentini M, Ding WX, Yue Z, Xie Y, Petersen M, Gewirtz DA, Mandell MA, Chu CT, Sinha D, Eftekharpour E, Zhivotovsky B, Besteiro S, Gabrilovich DI, Kim DH, Kagan VE, Bayir H, Chen GC, Ayton S, Lünemann JD, Komatsu M, Krautwald S, Loos B, Baehrecke EH, Wang J, Lane JD, Sadoshima J, Yang WS, Gao M, Münz C, Thumm M, Kampmann M, Yu D, Lipinski MM, Jones JW, Jiang X, Zeh HJ, Kang R, Klionsky DJ, Kroemer G, Tang D 05 Mar 2024, PMID: 38442890 Autophagy

Nakanoh S, Sham K, Ghimire S, Mohorianu I, Rayon T, Vallier L Mar 2024, PMID: 38427729 Science advances
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Group Leaders

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Simon Cook

ڹϳϱϹ Director

Della David

Group Leader

Oliver Florey

Group Leader

Phillip Hawkins

Group Leader

Nicholas Ktistakis

Group Leader

Ian McGough

Tenure Track Group Leader

Teresa Rayon

Tenure Track Group Leader

Rahul Samant

Tenure Track Group Leader

Hayley Sharpe

Group Leader

Len Stephens

Group Leader

Sophie Trefely

Tenure Track Group Leader

Honorary Group Leaders

Valerie O'Donnell

Honorary Group Leader

Associate Group Leaders

Heidi Welch

Associate Group Leader