Imperial College London is a public research university located in London, United Kingdom. As a former constituent college of the federal University of London, it became fully independent during the commemoration of its centenary on 9 July 2007. Imperial has grown through mergers, including with St Mary's Hospital Medical School , the National Heart and Lung Institute and the Charing Cross and Westminster Medical School . Imperial College Business School was established in 2003 and its building opened by the Queen of England in 2004.Imperial is organised into four main faculties: science, engineering, medicine and business; within the school there are over 40 departments, institutes and research centres. Imperial has around 13,500 students and 3,330 academic and research staff. Imperial's main campus is located in the South Kensington area of London, with additional campuses in Chelsea, Hammersmith, Paddington, Silwood Park, Wye College, and Singapore, making it one of the largest estates of any UK tertiary institution.Imperial is a major centre for biomedical research with the research staff having a total income of £822 million in 2012/13. Imperial is a founding member of the Francis Crick Institute and Imperial College Healthcare. Imperial is a member of the Association of Commonwealth Universities, the European University Association, the Association of MBAs, the G5, the League of European Research Universities, Oak Ridge Associated Universities and the Russell Group. Along with Cambridge and Oxford, Imperial, forms a corner of the "golden triangle" of British universities.Imperial is one of the most selective British universities. Imperial is consistently ranked among the top universities in the world, ranking 2nd in the 2014/15 QS World University Rankings and 9th in the 2014/15 Times Higher Education World University Rankings. In a corporate study carried out by The New York Times, its graduates were one of the most valued globally. Imperial's alumni and faculty include 15 Nobel laureates, 2 Fields Medalists, 70 Fellows of the Royal Society, 82 Fellows of the Royal Academy of Engineering, and 78 Fellows of the Academy of Medical science. Wikipedia.
Barnes P.J.,Imperial College London
Immunological Reviews | Year: 2011
Allergic inflammation is due to a complex interplay between several inflammatory cells, including mast cells, basophils, lymphocytes, dendritic cells, eosinophils, and sometimes neutrophils. These cells produce multiple inflammatory mediators, including lipids, purines, cytokines, chemokines, and reactive oxygen species. Allergic inflammation affects target cells, such as epithelial cells, fibroblasts, vascular cells, and airway smooth muscle cells, which become an important source of inflammatory mediators. Sensory nerves are sensitized and activated during allergic inflammation and produce symptoms. Allergic inflammatory responses are orchestrated by several transcription factors, particularly NF-κB and GATA3. Inflammatory genes are also regulated by epigenetic mechanisms, including DNA methylation and histone modifications. There are several endogenous anti-inflammatory mechanisms, including anti-inflammatory lipids and cytokines, which may be defective in allergic disease, thus amplifying and perpetuating the inflammation. Better understanding of the pathophysiology of allergic inflammation has identified new therapeutic targets but developing effective novel therapies has been challenging. Corticosteroids are highly effective with a broad spectrum of anti-inflammatory effects, including epigenetic modulation of the inflammatory response and suppression of GATA3. © 2011 John Wiley & Sons A/S.
Barnes P.J.,Imperial College London
Journal of Allergy and Clinical Immunology | Year: 2013
Reduced responsiveness to the anti-inflammatory effects of corticosteroids is a major barrier to effective management of asthma in smokers and patients with severe asthma and in the majority of patients with chronic obstructive pulmonary disease (COPD). The molecular mechanisms leading to steroid resistance are now better understood, and this has identified new targets for therapy. In patients with severe asthma, several molecular mechanisms have been identified that might account for reduced steroid responsiveness, including reduced nuclear translocation of glucocorticoid receptor (GR) α after binding corticosteroids. This might be due to modification of the GR by means of phosphorylation as a result of activation of several kinases (p38 mitogen-activated protein kinase α, p38 mitogen-activated protein kinase γ, and c-Jun N-terminal kinase 1), which in turn might be due to reduced activity and expression of phosphatases, such as mitogen-activated protein kinase phosphatase 1 and protein phosphatase A2. Other mechanisms proposed include increased expression of GRβ, which competes with and thus inhibits activated GRα; increased secretion of macrophage migration inhibitory factor; competition with the transcription factor activator protein 1; and reduced expression of histone deacetylase (HDAC) 2. HDAC2 appears to mediate the action of steroids to switch off activated inflammatory genes, but in patients with COPD, patients with severe asthma, and smokers with asthma, HDAC2 activity and expression are reduced by oxidative stress through activation of phosphoinositide 3-kinase δ. Strategies for managing steroid resistance include alternative anti-inflammatory drugs, but a novel approach is to reverse steroid resistance by increasing HDAC2 expression, which can be achieved with theophylline and phosphoinositide 3-kinase δ inhibitors. Long-acting β2-agonists can also increase steroid responsiveness by reversing GRα phosphorylation. Identifying the molecular mechanisms of steroid resistance in asthmatic patients and patients with COPD can thus lead to more effective anti-inflammatory treatments. © 2013 American Academy of Allergy, Asthma & Immunology.
Apperley J.F.,Imperial College London
The Lancet | Year: 2015
In less than 10 years, the prognosis of chronic myeloid leukaemia has changed from that of a fatal disease to a disorder amenable simply to lifelong oral medication and compatible with a normal lifespan. This change has been made possible by a deep understanding of the molecular pathogenesis and a determination to develop targeted and selective drugs. This Seminar summarises the presentation, pathophysiology, diagnosis and monitoring technology, treatment options, side-effects, and outcomes of chronic myeloid leukaemia, and discusses the possibility of cure - ie, stable undetectable or low level disease in the absence of medication. Chronic myeloid leukaemia continues to instruct us in the mechanisms of leukaemogenesis and provides hope not only for similar developments in management of other malignancies, but also for the remarkable speed with which these can move from bench to bedside.
Merkenschlager M.,Imperial College London |
Odom D.T.,University of Cambridge
Cell | Year: 2013
Current epigenomics approaches have facilitated the genome-wide identification of regulatory elements based on chromatin features and transcriptional regulator binding and have begun to map long-range interactions between regulatory elements and their targets. Here, we focus on the emerging roles of CTCF and the cohesin in coordinating long-range interactions between regulatory elements. We discuss how species-specific transposable elements may influence such interactions by remodeling the CTCF binding repertoire and suggest that cohesin's association with enhancers, promoters, and sites defined by CTCF binding has the potential to form developmentally regulated networks of long-range interactions that reflect and promote cell-type-specific transcriptional programs. © 2013 Elsevier Inc.
Leitinger B.,Imperial College London
Annual Review of Cell and Developmental Biology | Year: 2011
Collagen, the most abundant protein in animals, is a key component of extracellular matrices. Not only do collagens provide essential structural support for connective tissues, but they are also intimately involved in controlling a spectrum of cellular functions such as growth, differentiation, and morphogenesis. All collagens possess triple-helical regions through which they interact with a host of other proteins including cell surface receptors. A structurally diverse group of transmembrane receptors mediates the recognition of the collagen triple helix: integrins, discoidin domain receptors, glycoprotein VI, and leukocyte-associated immunoglobulin-like receptor-1. These collagen receptors regulate a wide range of behaviors including cell adhesion and migration, hemostasis, and immune function. Here these collagen receptors are discussed in terms of their molecular basis of collagen recognition, their signaling and developmental functions, and their roles in disease. © 2011 by Annual Reviews. All rights reserved.