Protein puzzle: Quest to explain how diseases develop

UK researchers are embarking on the world's largest study of proteins circulating in the human body to identify markers that put people at risk of serious illness , years before it develops. The UK Biobank Pharma Proteomics Project will allow researchers to determine through changes in protein levels in the blood how genes, lifestyle and environment cause illness. It is hoped the project will also pave the way for faster and more accurate blood tests to diagnose autoimmune conditions such as multiple sclerosis and Crohn's disease. Experts say the work will provide a “crucial piece in the jigsaw puzzle for scientists”, by investigating the potential role that thousands of proteins in the blood play in diseases that occur during mid-to-late life . The developing research field – known as population proteomics – has demonstrated huge potential for new methods for diagnosis and treatments. The project will measure up to 5,400 proteins in each of 600,000 samples, including those taken 15 to 20 years ago from 500,000 people in their early forties to late sixties, as well as second samples taken from 100,000 UK Biobank volunteers 10 to 15 years later. A spokeswoman for the project told The National that this will allow researchers to create a unique database detailing how changes to a person's protein levels over mid-to-late life influence disease. “The resulting data will accelerate the identification of new drug targets, as well as proteins that could be used as a foundation for diagnostic tests and predicting prognosis of individual disease,” she added. The UK Biobank is considered the world’s largest source of biomedical data for use in health research. It has been running for 15 years, collecting biological, health and lifestyle information from 500,000 UK volunteers. The data set is always growing, with additions including the world’s largest set of whole genome sequencing data, imaging data from 100,000 participants and a set of protein biomarkers from 54,000 participants. Scientists from universities, charities, companies and governments across the world have been able to apply to use the data to advance modern medicine, and drive the discovery of new preventions, treatments and cures since 2012. More than 20,000 researchers in more than 50 countries are using UK Biobank data and about 14,000 peer-reviewed scientific papers have been published as a result. Pilot data has already allowed researchers to identify proteins that are raised in patients who go on to develop dementia up to a decade before diagnosis and seven years before the diagnosis of certain cancers. “That pilot study has also shown new targets for disease, allowing the development by the pharmaceutical industry of new treatments that would otherwise never have been discovered,” Prof Sir Rory Collins, principal investigator and chief executive of UK Biobank, told BBC Radio 4 on Friday. “By going from this pilot study of 50,000 to measure all half million of the kind of altruistic British men and women who joined UK Biobank , we're going to get an enormous amount more information about how to prevent a much wider range of diseases and how to treat them much better.” The scaled-up project, which is backed by a consortium of 14 pharmaceutical firms, including Johnson & Johnson, AstraZeneca and Pfizer, will accelerate research into the causes of diseases, said Prof Naomi Allen, chief scientist at UK Biobank. “Having data on protein levels gives us a much more complete picture of how genes, lifestyle, exposure to environment cause disease through changes in proteins,” she said. “So it adds a crucial piece in the jigsaw puzzle for scientists to figure out how disease develops and gives us firm clues on what we can do to prevent and treat it.” Data from the pilot study has indicated that specific proteins are substantially elevated in people with conditions such as multiple sclerosis and Crohn's disease, as well as dementia. “So you can see how a simple blood test could be used to complement existing diagnostic measures in order to diagnose these types of diseases more accurately and perhaps more quickly,” Prof Allen said. Evidence from the pilot has also highlighted how some drugs can be repurposed to treat other conditions, she added. “Some proteins that are known to be important for immunity are related to developing a range of psychiatric conditions like schizophrenia, depression, bipolar disorder and so on. “And given there are drugs already available that specifically target some of these proteins that are used for other conditions, it presents a real opportunity for repurposing those existing drugs for these neuropsychiatric conditions. “The same has been shown for some chemotherapy drugs, in that some proteins associated with specific cancers already map on to existing chemotherapy drugs that are used for other cancer types.” It will take about a year to measure the protein levels in the first 300,000 participant blood samples. The proteomic data will be made available to UK Biobank-approved researchers in staggered releases from 2026, with the full data set expected to be added to the UK Biobank Research Analysis Platform the following year.

Protein puzzle: Quest to explain how diseases develop

UK Biobank project, the world’s largest study of blood proteins, could pave the way for new treatments