A new Discovery Research Platform launched today and funded by £9 million grant from Wellcome, will reveal deep insights into the inner world of cells, shedding new light on diseases and antimicrobial drug resistance. Image The Discovery Research Platform for Hidden Cell Biology (DRP-HCB), will tackle knowledge gaps in cell biology, technical limitations and investigative bias that have created research “blind spots”. The seven-year grant will aid the development of new techniques to discover the biological functions of understudied proteins, visualise the inner workings of cells in unprecedented detail, and explore rare cellular events. Image The new Discovery Research Platform for Hidden Cell Biology will reveal the functions of understudied proteins, visualise the inner workings of cells and explore rare cellular events Understanding Cells Over the past 100 years, scientists have made remarkable progress in understanding cells and proteins - the fundamental building blocks of all organisms - but there is still much to be discovered. The data revolution in biology is now fuelling new opportunities that could transform understanding of cells, from the inner workings of single-celled infectious bacteria to diverse human cell types. This knowledge is essential to understand living systems and underpins the development of new drugs and therapies to fight disease. Tackling Knowledge Gaps However, numerous ‘blind spots’ - areas of research that have remained intractable or unexplored - hamper progress. These knowledge gaps are known as Hidden Cell Biology. The DRP-HCB will encourage researchers from diverse disciplines to refocus cell biology towards neglected areas and major unsolved challenges that may have unexplored roles in health and disease. It will also focus on overcoming technical barriers, developing tools to produce new scientific insights and making it easier to analyse and access vast and varied datasets. Through these new techniques and collaborative research, the DRP-HCB plans to make understudied areas accessible to general research and medical communities. Protein characterisation The first human genome sequence led to a new era in basic research, offering the opportunity to better understand genes - the instructions for life - and the proteins they encode. Yet over 20 years later the function of many proteins remain unknown and 95% of research papers focus on only a quarter of human proteins. Often described as the workhorses of the cell, proteins have a role in almost every aspect of our biology and make up everything from the structures in our cells, muscles and bones to the hormones that carry messages around the body. However, thousands of human proteins are too small to be studied efficiently with current methods, so it remains unclear which roles they play in cells and human disease. The DRP-HCB will combine new technologies and research strategies to identify new proteins and reveal the functions of numerous understudied proteins. Rare events inside cells Rare events inside cells can cause changes that lead to drug resistance in infectious bacteria, fungi and parasites. In human cells, rare events can lead to changes that allow abnormal or damaged cells to grow and multiply when they shouldn't. These cells may form cancerous or benign tumours. If these changes inside cells enhance survival or provide other benefits, they can quickly spread and cause persistent infections or diseases that can be difficult to treat or life threatening. There is an urgent need to develop interventions to identify and tackle these rare events at the earliest possible stage to prevent or halt the progression of the disease. But rare events only happen in a small number of cells, are short-lived and involve complex processes, which make them difficult to detect using current methods. To tackle this the DRP-HCB will combine live tracking of multiple processes and parameters within cells by developing new approaches, including machine learning. This will allow observation of large numbers of cells and generate detailed information about how rare events arise as well as predicting how they may evolve or spread in cell populations. Atom to cell Over the last 50 years, advances in imaging techniques and basic research have revealed nanoscale structures inside cells and led to insights about protein structures and their complex interactions. However there is a disconnect between these nanoscale insights and how these structures and interactions make up the architecture of the whole cell and contribute to its essential functions. To tackle this the DRP-HCB will generate high-resolution maps of the molecular connections within various types of cells. This will reveal how nanoscale structures are organised inside cells and how proteins interact with each other and with other parts of the cell to carry out essential functions. New visualisation tools will be developed to aid understanding of vast and complex datasets allowing scientists to bridge the gap from identifying isolated structures and proteins to their organisation and roles inside the cell. This atom to cell approach will play a vital role in connecting the unexplored proteins and rare events, identified through DRP-HCB’s other research activities, to new health and disease insights. A website for DRP-HCB and further information will follow. About Discovery Research Platforms The DRP-HCB announcement is part of a £73 million initiative from Wellcome for eight new Discovery Research Platforms. Discovery Research Platforms are home to transformative research environments that will empower researchers to overcome specific barriers holding back progress in their various fields of research. The University of Edinburgh is the only institution in Scotland to receive a Discovery Research Platform award from Wellcome. By bringing together diverse expertise and technology to focus on neglected areas of cell biology, our Discovery Research Platform for Hidden Cell Biology represents a new approach to discovery research, I am excited to see the new scientific fields and insights into disease mechanisms that emerge as our Platform re-defines the research landscape. Professor Adele MarstonProfessor of Cell Biology and Director of the DRP-HCB, School of Biological Sciences I am delighted to see the establishment of our Discovery Research Platform for Hidden Cell Biology and I’d like to thank Wellcome for their ongoing and visionary support. Combining our current expertise in cell biology with fresh academic and technical input promises to accelerate future scientific breakthroughs in this field to benefit all. Professor Peter MathiesonPrincipal and Vice-Chancellor of the University of Edinburgh Discovery Research Platforms are a brand-new approach for Wellcome. By providing substantial support focused on specific research challenges, these environments have the potential to revolutionise fields and provide maximum possible benefit for researchers around the world. I am particularly excited that Discovery Research Platforms span such an exciting range of disciplines, showcasing our increasingly inclusive approach to funding. Michael DunnDirector of Discovery Research at Wellcome Related Links Wellcome Centre for Cell Biology Wellcome Press Release - From cells to societies – £73m for transformative research environments to break down barriers Publication date 30 Nov, 2023