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Cambridge, United Kingdom

The Babraham Institute, is an independent charitable life science institute involved in biomedical research, set in an extensive parkland estate just south of Cambridge. Its current director is Prof. Michael Wakelam. Wikipedia.

Linterman M.A.,Babraham Institute
Immunology and Cell Biology | Year: 2014

Normal ageing is accompanied by a decline in the function of the immune system that causes an increased susceptibility to infections and an impaired response to vaccination in older individuals. This results in an increased disease burden in the aged population, even with good immunisation programmes in place. The decreased response to vaccination is partly due to the diminution of the germinal centre response with age, caused by impaired T-cell help to B cells. Within the germinal centre, T-cell help is provided by a specialised subset of CD4 + T cells; T follicular helper (Tfh) cells. Tfh cells provide survival and selection signals to germinal centre B cells, allowing them to egress from the germinal centre and become long-live plasma cells or memory B cells, and provide life-long protection against subsequent infection. This review will discuss the cellular and molecular changes in both Tfh cells and germinal centre B cells that occur with advancing age, which result in a smaller germinal centre response and a less effective response to immunisation. © 2014 Australasian Society for Immunology Inc. Source

Berridge M.J.,Babraham Institute
Biochemical Society Transactions | Year: 2012

A wide range of Ca 2+ signalling systems deliver the spatial and temporal Ca 2+ signals necessary to control the specific functions of different cell types. Release of Ca 2+ by InsP 3 (inositol 1,4,5-trisphosphate) plays a central role in many of these signalling systems. Ongoing transcriptional processes maintain the integrity and stability of these cell-specific signalling systems. However, these homoeostatic systems are highly plastic and can undergo a process of phenotypic remodelling, resulting in the Ca 2+ signals being set either too high or too low. Such subtle dysregulation of Ca 2+ signals have been linked to some of the major diseases in humans such as cardiac disease, schizophrenia, bipolar disorder and Alzheimer's disease. © The Authors Journal compilation © 2012 Biochemical Society. Source

Within the lymphocyte lineages, restriction of immunoglobulin V(D)J recombination to B cells and T cell receptor (TCR) recombination to T cells is governed by a myriad of epigenetic mechanisms that control the chromatin accessibility of these loci to the Rag recombinase machinery in a lineage and developmental stage-specific manner. These mechanisms operate both locally at individual gene segments, and globally over large chromatin domains in these enormous multigene loci. In this review we will explore the established and emerging roles of three aspects of epigenetic regulation that contribute to large-scale control of the immunoglobulin heavy chain locus in B cells: non-coding RNA transcription, regulatory elements, and nuclear organization. Recent conceptual and technological advances have produced a paradigm shift in our thinking about how these components regulate gene expression in general and V(D)J recombination in particular. © 2010 Elsevier Ltd. Source

Fearnley C.J.,Babraham Institute
Cold Spring Harbor perspectives in biology | Year: 2011

Calcium (Ca(2+)) is a critical regulator of cardiac myocyte function. Principally, Ca(2+) is the link between the electrical signals that pervade the heart and contraction of the myocytes to propel blood. In addition, Ca(2+) controls numerous other myocyte activities, including gene transcription. Cardiac Ca(2+) signaling essentially relies on a few critical molecular players--ryanodine receptors, voltage-operated Ca(2+) channels, and Ca(2+) pumps/transporters. These moieties are responsible for generating Ca(2+) signals upon cellular depolarization, recovery of Ca(2+) signals following cellular contraction, and setting basal conditions. Whereas these are the central players underlying cardiac Ca(2+) fluxes, networks of signaling mechanisms and accessory proteins impart complex regulation on cardiac Ca(2+) signals. Subtle changes in components of the cardiac Ca(2+) signaling machinery, albeit through mutation, disease, or chronic alteration of hemodynamic demand, can have profound consequences for the function and phenotype of myocytes. Here, we discuss mechanisms underlying Ca(2+) signaling in ventricular and atrial myocytes. In particular, we describe the roles and regulation of key participants involved in Ca(2+) signal generation and reversal. Source

Berridge M.J.,Babraham Institute
Journal of Physiology | Year: 2014

Alzheimer's disease (AD) begins with a decline in cognition followed by neuronal cell death and dementia. These changes have been linked to a deregulation of Ca2+ signalling caused by a progressive increase in the resting level of Ca2+, which may influence cognition by interfering with the rhythm rheostat that controls the sleep/wake cycle. The rise in resting levels of Ca2+ may not alter the processes of memory acquisition during consciousness (gamma and theta rhythms), but may duplicate some of the events that occur during the slow oscillations responsible for the twin processes of memory consolidation and memory erasure that occur during sleep. The persistent elevation in the resting level of Ca2+ induced by an accumulation of amyloid β (Aβ) oligomers duplicates a similar small global elevation normally restricted to the period of slow oscillations when memories are erased during sleep. In AD, such a rapid erasure of memories soon after they are acquired during the wake period means that they are not retained for consolidation during sleep. The Aβ deregulates Ca2+ signalling through direct effects on the neurons and indirectly by inducing inflammatory responses in the microglia and astrocytes. Some of these deleterious effects of Aβ may be alleviated by vitamin D. © 2013 The Physiological Society. Source

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