The Francis Crick Institute

How are the different types of cells that comprise tissues produced? How are these cells arranged in the correct spatial and temporal patterns to form functional organs? What determines the size and shape of tissues and how is this maintained in the adult?

An understanding of the developmental and stem cell mechanisms underlying these fundamental life processes is essential for tackling a wide range of congenital and acquired diseases. Work at the Crick in this challenging area encompasses a wide variety of model organisms, biological scales and methodologies.

At the cellular scale, we seek to understand how cells become individualized and polarised and how they respond to signals from their neighbours and the extracellular environment.

At larger scales, we investigate how individual cells coordinate their behaviour to build complex tissues that regulate the morphology, physiology and behaviour of the whole organism. Adult organs are maintained and renewed by stem cell populations, and we study how stem cell behaviour is controlled to produce the full repertoire of differentiated cells and to respond to changing environmental demands.

In our work we take advantage of a variety of invertebrate and vertebrate animal species as well as cultured human cells and organoids. Our approaches span disciplines such as genetics, physiology, cell and molecular biology, biochemistry, biophysics, mathematics and computational biology. Recent advances underscore the importance of stem cells in regenerative medicine and as the cells of origin in many cancers. Increasing evidence highlights the impact of development upon adult health and disease.

Our work seeks to understand the principles of development, to use this knowledge to shed light on diseased and damaged tissues and to develop new therapeutic approaches.

Cells are built from biological macromolecules. These macromolecules come together in dynamic assemblies that form all cellular constituents and execute a plethora of intricate functions.

They also form the control networks that orchestrate cell behaviour. Human disorders are invariably caused by changes in how biological macromolecules are encoded, or how they function in cells.

The Genes to Cells Interest Group studies the principles by which molecules give rise to cellular function. The group uses diverse methodologies, ranging from atomic structures, biochemistry and molecular genetics to the direct observation of subcellular and cellular behaviour. Our experimental systems range from bacteria to humans. Current areas of interest include molecular mechanisms of genome maintenance, gene expression and protein biogenesis, as well as the cell biology of cell division, cytoskeletal, organelle and membrane function.

Our wide-ranging expertise provides a holistic view of molecular cell biology, thereby accelerating scientific discovery and clinical translation opportunities. We collaborate extensively and across research disciplines, delivering profound insight and high-profile research outputs. We inspire and engage the public by sharing our fascination of molecules and cells, the building blocks of all life.

It is estimated that around a quarter of all deaths in the world result from infectious diseases.

Among these, the top three killer agents are HIV-1,Mycobacterium tuberculosis (Mtb) and the malaria parasite. Viruses causing respiratory infections also feature prominently as well as other parasites like Toxoplasma that cause serious infections of the unborn child or immunocompromised patients.

Such infectious agents are the main topics for study within laboratories comprising the Host and Pathogen Interest Group. Work from our laboratories is focussed on understanding the growth, metabolism, pathogenicity, antimicrobial action and resistance, and evolution of these agents as well as host responses to infection.

Our studies have direct relevance regarding efforts to limit the spread of the disease agents and to reduce their effects with novel drugs as well as facilitating their diagnosis and improving judgements regarding prognosis. Members of the Host and Pathogen Group make very real contributions to international efforts to improve global health, fully consistent with the Crick's mission.

We collaborate on a worldwide basis and publish a significant number of high profile studies, we provide information vital for setting public policy, we help inform public perceptions of global health problems and we continue to assist in the development of new methods for preventing the spread of infectious agents of disease. 

The nervous system controls the interaction of organisms with their environment and maintains the activity of vital organs in the body.

Understanding how functional neuronal ensembles emerge during development, how they process information from the outside world and govern our activities in it, and how they respond to environmental challenges, injury or disease to maintain a healthy state, remain major challenges of this century.

Our diverse and interactive research programmes in the Neuroscience interest group (NeurIG) address these fundamental questions in different experimental model organisms (mice, zebrafish and Drosophila) and a range of genetic, imaging and electrophysiological recording methodologies. In particular, we aim to understand the mechanisms that control neural stem cell function and how multiple neuronal and glial cell types are generated during development and maintained throughout life. We seek to identify the molecular pathways implicated in the formation of specialised anatomical and functional domains of the nervous system and understand how axons and dendrites are assembled into functional neural circuits. Our studies focus on uncovering the properties of neural circuits dedicated to sensory information processing, including olfaction and vision. We investigate how neuronal networks generate complex behaviours and control homeostatic body functions, such as sleep and food intake. Finally, we explore how the integrated activity of the nervous and immune systems contributes to defense against pathogens and maintains homeostasis.

These studies are highly relevant for elucidating the pathogenetic mechanisms of neurodevelopmental, neurodegenerative and other common disorders and provide a rational basis for the development of innovative therapeutic strategies.

The immune system has evolved to protect the organism from pathogens and to detect and eliminate tissue cells that are undergoing stress or malignant transformation.

These defensive actions need to be highly specific and tightly controlled in their magnitude, to avoid immune-mediated tissue damage and morbidity as found in allergies and autoimmune disease.

These topics are the focus of work in the laboratories making up the Immunology Interest Group at the Francis Crick Institute. Immunologists at the Crick investigate the development and activation of immune cells, signalling pathways involved in inflammation and immune responses, the immunology of mucosal body barriers such as the skin, gastrointestinal and respiratory tract, and cancer immunology.

The pathogens and infectious diseases under study range from malaria, toxoplasma, retroviruses, tuberculosis to influenza and helminth infections. Autoimmune and autoinflammatory diseases like multiple sclerosis, psoriasis, colitis and allergies are another focus of the Immunology Interest Group, as well as understanding how anti-cancer immune responses function.

These diseases represent a major burden to human health and wealth, and immunologists at the Crick work hard to understand better the immune mechanisms at work, to enhance, improve and control immune responses and thus make a difference to global health. Our research work is based on world-wide collaborations, published widely, and involves extensive outreach to the public and training of future immunologists.

The Structural Biology Interest Group comprises a wide and diverse grouping of research teams that share the common goal of describing cellular function at the atomic and mechanistic level.

The biological themes under investigation reflect the wide range of research areas covered within the Crick. These include mechanisms of cellular and immune signalling, the structural biology of epigenetic regulation, DNA repair and chromosome segregation and viral assembly and infection.

To study this diverse range of systems we employ a battery of complementary biochemical, biophysical, computational and structural techniques that include, but are not limited to, X-ray crystallography, NMR spectroscopy, cryo-electron microscopy and combined spectroscopic, thermodynamic and hydrodynamic methodologies.

Our overarching goal is to understand complex biological phenomena in terms of the molecular interactions that drive and regulate them. These efforts are underpinned by a desire to open up new approaches to combat disease and many of the groups are actively involved in efforts to translate structural biology research into new medicines and treatments that will impact on global health.

Cancer touches the lives of almost everyone. A key goal of the Francis Crick Institute is to understand why cancer develops and to find new ways to treat, diagnose and prevent it.

Cancer is a highly complex disease that is driven by mutations and complex genomic rearrangements within tumour cells. Typically, these mutations arise during the lifetime of the patient; however, in some cases they may be inherited. A key focus of research at the Crick is to understand how mutations arise and how they perturb the proliferation, metabolism, response to signals, survival, cell migration, and how these cells evade immune surveillance.

The behaviour of cancer cells is further determined by other cells within the body, some of which counteract cancer phenotypes and others that promote cancer spread and therapy failure. The power of these non-cancerous cells is exemplified by the recent success of therapies that re-awaken the immune system to target tumours. Cancer research at the institute spans basic biology to cutting-edge analysis of patient material from clinical trials.

The inclusion of immunology, development biology, and other disciplines under one roof at the Francis Crick Institute enables a multi-faceted approach to further understanding of all aspects of cancer, from its initiation to its response to therapy. This Gateway Area houses work produced by the Cancer Interest Group at the Francis Crick Institute.