Wed, 21/05/2025 - 15:20
Proteostasis, the myriad mechanisms that ensure our proteins work correctly, is key to healthy ageing. We speak to Dr Della David and Dr Rahul Samant about their cutting-edge research, why proteostasis is such a growing area of strength at the 果酱视频, and how the new will help accelerate research in the field.
In understanding health and disease, it鈥檚 impossible to overstate the importance of proteins. The smooth working of a plethora of proteins鈥攖he so-called proteome鈥攅nsures that our cells function correctly and can adapt to a changing environment. That鈥檚 why proteostasis鈥攖he quality control mechanisms that keep proteins working properly鈥攊s a burgeoning field of research.
Many diseases鈥攑articularly those of ageing鈥攕tem from problems in proteostasis and the breakdown of proteostasis is recognised as a hallmark of ageing itself. Dr Della David, one of several group leaders at the 果酱视频 who focuses on proteostasis, uses the tiny nematode Caenorhabditis elegans to discover mechanisms to help combat age-related diseases and promote healthy ageing.
鈥淜eeping the integrity of your proteome is really challenging but so important for life; every organism needs these mechanisms that protect the proteome. These mechanisms look after the proteins, make sure they function at the correct location, and ensure their disposal when they become damaged or aggregate, so proteostasis is absolutely fundamental and poor proteostasis accelerates the ageing process,鈥 she explains.
Dr Rahul Samant, also a group leader in the Signalling programme, works on cellular senescence, another hallmark of ageing. As we age, accumulation of damage鈥攊ncluding through proteostasis faults鈥攃auses a build up of large cells that have lost their intended function in our tissues. No longer able to divide or regenerate but persistent and hard to kill, these so-called zombie cells accumulate in ageing tissues causing chronic inflammation.
鈥淔ifteen years ago it was unclear whether these cells were a cause of ageing or just correlated with it. Then, researchers genetically engineered a mouse with no zombie cells and found they not only lived longer but were healthier,鈥 he says. The same has since been found in other species and researchers are working to unravel the fundamental biology to explain why.
Using a range of different human cell types, Samant is looking at how the same senescence stress drives diverse responses in proteostasis. 鈥淎t first, our question was highly focused: if you introduce this stress, what happens to the molecular circuitry? In fact, there are diverse responses, so we are looking at whether there is more commonality in all types of senescent cells in our body rather than in senescent and non-senescent cells of the same type.鈥
This understanding will be crucial to drug discovery, he says. 鈥淲e always look for magic bullets 鈥 drugs that will kill every senescent cell in the body. Some think we鈥檒l be able to find this if we look harder. Others think there is no unifying factor and that multiple treatment options will be needed depending on the exact type of senescence driving that disease.鈥
Answering such challenging questions demands different perspectives and solid technical capabilities, he says. 鈥淒iversity is important for understanding ageing and proteostasis better, that鈥檚 one of the 果酱视频鈥檚 great strengths. I don鈥檛 know anywhere else working on proteostasis across such a diverse set of organisms, including yeast, worms, flies, mice and human cells. The other key strength is the breadth of our expertise, both scientifically in our research groups, but also of the technical staff in our facilities.鈥
鈥淔or example, we work really closely with the mass spectrometry facility at the 果酱视频. For us, the facility is not simply a service, they are partners we actively collaborate with. The same is true with bioinformatics. It鈥檚 an iterative process built on two-way communication. It's one of the main reasons I joined the 果酱视频,鈥 explains Samant.
Another example of the 果酱视频鈥檚 leadership role and collaborative ethos is the UK Proteostasis Network, established in 2024 with David and colleague Dr Oliver Florey as two of its cofounders. 鈥淭he aim is to bring the UK proteostasis community together, hold events and empower early career researchers because although the UK has great strengths in proteostasis research, we could achieve even more by sharing ideas and expertise,鈥 David explains.
During its first 12 months, the Network has gone from strength to strength. Its first two-day meeting in Spring 2024 attracted 170 attendees from academia and industry and a second will follow in 2025 鈥 evidence of the community鈥檚 huge enthusiasm to work together and build the Network.
鈥淚ndividual groups are doing amazing work and I鈥檓 super excited about animal and plant scientists working together to cross pollinate ideas,鈥 she concludes. 鈥淎nd now is absolutely the right time. We have a clear view of what we need to discover. We are at a critical moment to bring the community together and realise its potential.鈥
21 May 2025
By Becky Allen