On 22 July 2026, members of the UK proteostasis research community gathered at the Institute of Cancer Research, London, for the Proteostasis UK Sandpit 2026. Designed to foster new connections and stimulate innovative collaborative ideas, the event brought together researchers from a diverse range of disciplines and career stages for a day of interactive discussion, team-building, and project development.
Participants worked together to generate and refine novel project ideas, with teams developing proposals aimed at addressing key questions within the field. Following a competitive review process, several outstanding proposals were selected for seed funding.
We are delighted to announce that three proposals developed through the Sandpit were subsequently awarded funding.
The funding of all three projects is a testament to the quality of ideas generated during the event and demonstrates the value of bringing together diverse expertise from academia, industry, and across biological systems. These new collaborations have the potential to generate exciting discoveries, establish lasting partnerships, and create a strong foundation for future larger-scale funding applications.
The success of the Sandpit highlights the creativity, enthusiasm, and collaborative spirit of the UK proteostasis community. We look forward to following the progress of these projects and sharing their outcomes with the network in the months ahead.
Proteostasis UK would like to thank all participants for their energy, openness, and willingness to engage in the collaborative process, which made the event such a productive and inspiring success.
Lead: Viktor Korolchuk (Newcastle University)
Collaborating partners: Frederica Theodoulou (Rothamsted Research), Kishor Ingole (Kathryn Lilley's group at University of Cambridge), Max Brown (Procter & Gamble)
Summary:
Living organisms must continually adapt to changes in oxygen availability while maintaining healthy and functional cells. In plants, flooding deprives tissues of oxygen and is followed by a burst of oxidative stress when water recedes. Mammalian tissues experience a similar challenge during ischaemia-reperfusion injury, where restoration of oxygen supply can itself damage mitochondria. In both cases, successful recovery depends on restoring a healthy population of mitochondria, yet the mechanisms that coordinate this process remain poorly understood.
Mitophagy, a specialised form of autophagy that selectively removes damaged mitochondria, is an attractive candidate mechanism for promoting recovery from oxygen stress. Although mitophagy has been described in both plants and mammals, it remains unclear whether it contributes to adaptation during oxygen deprivation, reoxygenation, or both, and whether common principles operate across these evolutionarily distant kingdoms.
This project brings together expertise in plant biology, mammalian autophagy, proteomics and spatial proteomics to compare mitochondrial adaptation during submergence-reoxygenation in plants and hypoxia-reoxygenation in human cells. We will determine when mitophagy is activated, assess how mitochondrial function changes during recovery, and integrate these findings with comparative proteomic analyses to identify conserved molecular pathways associated with successful recovery.
By generating the first direct cross-kingdom comparison of mitochondrial adaptation during oxygen stress and recovery, this pilot will establish whether mitophagy represents a conserved mechanism promoting recovery from environmental stress and provide the foundation for future mechanistic studies of mitochondrial quality control and proteostasis.
Lead: Yu Ye (Imperial College London)
Collaborating partners: Cara Croft (Queen Mary University of London), Nick Robinson (University of Lancaster), Adam Grieve (University of Bristol), Jasmeen Oberoi (University of Sussex), Sobia Hamid (Infinicell Bio)
Summary:
To maintain a healthy protein balance, cells depend on molecular machines called proteasomes to break down damaged or unwanted proteins, recycling them into biological building blocks. Proteasomes can be thought of as recycling bins — cells use several related forms that differ in core structure to break down specific waste/unwanted proteins. Core structures can be covered with regulatory caps, like bin lids that determine how fast protein waste enters the bin. This results in a multitude of proteasome forms that handle cellular protein breakdown.
Proteasome forms vary across cell types; this may help explain why some cells cope better than others with the protein damage linked to conditions such as neurodegeneration and cancer. However, how this balance between proteasome forms is established and how it regulates protein recycling remains unknown. This matters because sensitively controlling protein levels at specific locations within a cell is fundamental to regulating virtually all biological processes.
Our team will investigate how different human cell types organise their proteasomes, and how these principles compare across diverse branches of life. We have developed a sensitive platform that enables us to quantify different proteosome forms present within the different cell types. We will challenge the cells with a mild stress and track how their proteasome composition and distribution changes in response. This pilot will generate the first cross-kingdom, cross-cell-type comparative map of proteasome abundance and stress-responsive distribution, providing proof-of-principle data for investigating the general rules that govern proteasome behaviours in health and disease.
Lead: Harvey Johnston (Cambridge Institute for Medical Research)
Collaborating partners: Frederica Theodoulou (Rothamsted Research), Urvashi Thacker (Syngenta)
Summary:
All organisms require resilience against sudden increases in environmental temperature—a stress known as heat shock. Characterising cellular responses to heat shock provides vital insights into how organisms maintain a healthy balance of protein production and breakdown, a process termed proteostasis. As global temperatures rise, understanding these mechanisms offers important implications for protecting species, such as food crops, and predicting how diverse organisms adapt to more frequent thermal stress.
We propose evaluating how species spanning almost all kingdoms of life, which live at very different environmental temperatures, have evolved to tolerate and react to transient, acute, but non-lethal heat shock. To achieve this, we will combine samples from 11 organisms and expertise from 9 institutions with state-of-the-art analytical tools—which measure thousands of cellular proteins simultaneously. Specifically, we will use a new methodology developed by the lead applicant, ‘Ubi-SCAPE’, which purifies proteins tagged with chains of a small molecule called ubiquitin (‘poly-ubiquitylation’), which typically marks proteins for disposal. These observations will capture a unique, early snapshot of the rapid protection mechanisms organisms use before protein degradation occurs.
This work will be conducted on species from across the Proteostasis UK network, including plants from hot and cold climates, Antarctic plunderfish, yeast, single-celled protists, algae, archaea, nematode worms, fruit flies, and brain cells from rats, naked mole rats, and humans.