Our research combines the traditional disciplines of Anatomy and Physiology alongside innovative research programmes in Animal Models of Human Disease, Stem Cells, Neuroscience and Regenerative Medicine.
Our academic staff are experts in their fields and have provided consultancy advice to industry, research councils and charities; their research agendas are relevant to many human diseases and in areas of interest to the pharmaceutical and biotech industries.
Several staff have ongoing collaborations with companies; interactions with industry are welcomed and encouraged and they have both allowed the pursuit of new research directions and progressed translational research.
Our research comprises four interdisciplinary themes (click title to expand for further information) each linked to our research centres.
|Lifecourse Biology (Bateson Centre)||
Two fundamental challenges of the 21st century are to understand Life, and to understand the Biology of Disease. In the Bateson Centre we are addressing these two globally-significant challenges through a strong partnership between basic developmental biologists and clinicians. Our shared aims are to understand how the body develops and how the body changes over the lifecourse.
At one end of our research spectrum, we tackle the question of how our bodies are built, and how our bodies adapt to the changing needs of life, coping with ongoing stress and change that naturally occur through life. Our bodies are made up of millions of cells, which work, with concordance and integrity, as an individual being. And throughout life, tissue and organs are not just built, but restored and regenerated.
We use developmental, genetic and imaging approaches in simple animal model organisms and 3-dimensional organ cultures. These allow us to perform real-time imaging of cells and tissues in living systems and examine how co-ordinated and integrated changes in cell fate, shape and behaviour sculpt the tissues and organs that form our complex bodies and brains. The same model organisms and resources enable us to explore the dynamic, changing landscape of the body throughout life, and enable us to tackle wide-ranging questions of critical importance: How does the body stay the same, faced with the dramatic changes and demands of life? How does the body alter when required? How does the body age?
At the other end of our research spectrum, we study disease, degeneration and decline, all of which occur when the normal balance – the homeostasis – of the body is compromised. We explore clinical problems that pose major health burdens to our society, including cancer, cardio-vascular disease, chronic inflammatory diseases and degenerative diseases of the nervous and musculo-skeletal systems. The simple model organisms that we use provide stunning tools to visualise diseased and degenerating systems in real time, and to identify and then characterise the roles that different genes, proteins and cells play during these processes.
A key aim of Bateson Centre scientists is to rapidly translate basic research findings into clinical applications. Our Small Molecule Screening Unit and the Sheffield RNAi Screening Facility aid such translation by providing the means to screen for small molecules that can modulate disease progression in model organisms. The insights obtained from these screens act as a springboard to develop new therapies for diseases.
|Membrane Biology (Centre for Membrane Interactions and Dynamics)||
The Centre for Membrane Interactions and Dynamics (CMIAD) is a virtual University Centre which brings together cell biologists investigating the basic mechanisms underpinning membrane traffic and cytoskeletal dynamics with physical scientists, computational biologists and clinicians with the ultimate aim of developing improved therapies. It is estimated that approximately 30% of the human genome encodes membrane proteins. Membrane trafficking ensures that these proteins are sorted and targeted to their correct destinations within cells so that they can function correctly.
The cytoskeleton is a 'skeleton' made of protein, which is found inside cells and plays key roles in the movement of material during membrane trafficking, migration and cell division. As such mechanisms of membrane trafficking and cytoskeletal rearrangements underlie almost all biological processes at the cellular, tissue and organismal level and defects give rise to diseases including cancer, neurodegeneration, muscular dystrophy, diabetes, and heart disease. Our main research is focused around the basic biology of endocytosis, exocytosis, synaptic mechanisms and membrane-cytoskeletal interactions in tissue culture cell lines as well as animal models including Drosophila and Zebrafish. These systems lend themselves to our existing screening technologies and to quantifiable computational modelling.
We interact with clinicians in the Faculty of Medicine, Dentistry and Health to facilitate the translation of our fundamental findings into the clinic. We also interact with physical scientists, especially in the development of super resolution microscopy
|Sensory Neuroscience (Centre for Sensory Neuroscience)||
In Sensory Neuroscience we focus on how sensory systems represent the world to facilitate the guidance and adaptation of communication and movement in health and disease. Biomedical research has evolved very rapidly over the last few decades to provide insights into the molecular basis of sensory transduction, transfer of information to the central nervous system and human behaviour. Technical developments in electrophysiology, imaging and computational modeling, combined with human stem cell biology and the development of tractable animal models for in vivo studies, have started to bridge the gaps between molecular physiology, systems physiology, behaviour and therapy. All of these advances have potent applications for the treatment of human disease and to the production of medical devices.
The Centre for Sensory Neuroscience provides an exciting interface with the BMS Centre for Stem Cell Biology (CSCB), the Centre for Membrane Interaction and Dynamics (CMIAD) and the Bateson Centre, as well as the University’s Institute for In Silico Medicine (INSIGNEO).
In hearing we study development, function and potential regeneration of the vertebrate auditory and vestibular systems using in vitro cell lines, human stem cells and in vivo animal models of human hearing loss. In vision we work primarily with fly and fish models that allow us to use genetic models to study sensory information processing from photoreceptors to neural networks and animal behaviour. In the somatosensory system we use isolated cells and animal models of human disease to study the physiology and pharmacology of neuro-immune interactions in Inflammatory Bowel Disease (IBD) and Asthma. We study epithelial transport and barrier function, the mechanisms that lead to immune cell activation and resolution and the role of inflammatory mediators in neural activation, for example in pain signalling.
|Stem Cells and Cancer (Centre for Stem Cell Biology)||
The Centre for Stem Cell Biology (CSCB) brings together researchers focused on developing the basic biology and technology that will underpin the use of human Pluripotent Stem Cells for applications in medicine, whether for a direct use in regenerative medicine, or for disease modelling, drug discovery and toxicology. Our research exploits many aspects of molecular cell biology and developmental biology and so interfaces with other research in these areas in the Department. We also collaborate with other groups within the University, notably in the Centre for Signal Processing and Complex Systems in the Department of Automatic Control and Systems Engineering, nationally, with groups linked to the UK Regenerative Medicine Platform and internationally, for example to the EU Consortium, Plurimes, the EU Consortium Otostem and the International Stem Cell Initiative.
Embryonic stem (ES) cells correspond to cells that are found in the very early embryo and are capable of initiating differentiation leading to all cell types found in the adult body. They are said to be ‘Pluripotent’. Human ES cells, which can be maintained indefinitely in culture, were first isolated in 1998, following decades of work with corresponding mouse cells and with similar cells found in teratocarcinomas, a rare tumour that caricatures the processes of early embryonic development.
An alternative route to such cells was discovered in 2006, when it was found that fully differentiated adult cells could be converted back to cells closely resembling ES cells. Such cells were called induced pluripotent stem cells, or iPS cells. Collectively, ES and iPS cells are now known as PSC. It is the ability of these cells to differentiate into a very wide range of functional cell types that leads to the current excitement about their possible medical applications. To address this, researchers in the CSCB have derived over 20 new human ES cell lines, many in our GMP laboratory to standards that will facilitate their use in regenerative medicine.
Other work is focused upon the mechanisms by which PSC choose alternative fates, either dividing to generate more undifferentiated cells (‘Self-Renewal’), or choosing between pathways that lead to many distinct differentiated cell types. Among such differentiated cells are specialized cells that function in the ear, and recent work in the CSCB has shown that auditory neurons derived from human PSC can be transplanted to allow recovery of hearing in an animal model. A further aspect of PSC is their acquisition of mutations that influence their behavior. While we are seeking to understand mutational the mechanisms in these cells, to minimize the appearance of variants, we are also exploiting those variants that do arise as to explore aspects of stem cell biology pertinent to cancer.