探花直播 of Cambridge - Sergey Nejentsev
/taxonomy/people/sergey-nejentsev
enGene discovery provides clues to how TB may evade the immune system
/research/news/gene-discovery-provides-clues-to-how-tb-may-evade-the-immune-system
<div class="field field-name-field-news-image field-type-image field-label-hidden"><div class="field-items"><div class="field-item even"><img class="cam-scale-with-grid" src="/sites/default/files/styles/content-580x288/public/news/research/news/150316tb.jpg?itok=EMdHz9Aj" alt="Mycobacterium tuberculosis" title="Mycobacterium tuberculosis, Credit: NIAID" /></div></div></div><div class="field field-name-body field-type-text-with-summary field-label-hidden"><div class="field-items"><div class="field-item even"><p>TB, caused by infection with the pathogen Mycobacterium tuberculosis, is a major global public health problem. According to the World Health Organization, in 2013 nine million people fell ill with TB and 1.5 million died from the disease. Over 95% of TB deaths occur in low- and middle-income countries. About one-third of the world's population has latent TB 鈥� in other words, they carry the infection but show no symptoms; only around one in ten of infected individuals develop active TB.<br /><br />
Evidence suggests that an individual鈥檚 DNA affects their susceptibility to TB, both in terms of becoming infected and whether the disease progresses from latent to active TB. In order to identify genes that predispose people to TB, an international team of researchers carried out a genome-wide association study (GWAS), comparing the genomes of 5,500 TB patients against those of 5,600 healthy controls. In total, the researchers analysed 7.6 million genetic variants.<br /><br />
探花直播team found that variants of the gene ASAP1 on chromosome 8 affect individuals鈥� susceptibility to TB. 探花直播gene encodes a protein carrying the same name and is highly expressed 鈥� in other words, larger amounts of the protein are found 鈥� in a particular type of immune cells known as dendritic cells that play a key role in kick-starting the body鈥檚 immune response to incoming pathogens.<br /><br />
探花直播researchers showed that infection with M. tuberculosis leads to the reduction of ASAP1 expression in dendritic cells 鈥� but people who have a particular genetic variant in the ASAP1 gene associated with greater susceptibility to TB show stronger reduction of ASAP1 expression after infection than people who have a protective variant of this gene.<br /><br />
探花直播researchers found that reducing levels of the ASAP1 protein affects the ability of dendritic cells to move, which explains the mechanism of the previously-known slow migration of dendritic cells infected with M. tuberculosis and may help the pathogen to evade the immune system, leading to TB.<br /><br />
鈥淥ur study provides a new insight into biological mechanisms of TB,鈥� says Dr Sergey Nejentsev, Wellcome Trust Senior Research Fellow from the Department of Medicine at the 探花直播 of Cambridge, who led the research. 鈥淭B is a major global health problem and the threat of drug-resistance means that we urgently need to develop new ways of fighting back. In future, it may be possible to target immune pathways that involve ASAP1 to design efficient vaccines for TB prevention.鈥�<br /><br />
探花直播study was supported by the Wellcome Trust, EU Framework Programme 7, European Research Council, the Royal Society and the NIHR Cambridge Biomedical Research Centre.</p>
</div></div></div><div class="field field-name-field-content-summary field-type-text-with-summary field-label-hidden"><div class="field-items"><div class="field-item even"><p><p> 探花直播largest genetic study of tuberculosis (TB) susceptibility to date has led to a potentially important new insight into how the pathogen manages to evade the immune system. Published today in the journal Nature Genetics, the study advances understanding of the biological mechanisms involved in TB, which may open up new avenues to design efficient vaccines for its prevention.</p>
</p></div></div></div><div class="field field-name-field-content-quote field-type-text-long field-label-hidden"><div class="field-items"><div class="field-item even">TB is a major global health problem and the threat of drug-resistance means that we urgently need to develop new ways of fighting back</div></div></div><div class="field field-name-field-content-quote-name field-type-text field-label-hidden"><div class="field-items"><div class="field-item even">Sergey Nejentsev</div></div></div><div class="field field-name-field-image-credit field-type-link-field field-label-hidden"><div class="field-items"><div class="field-item even"><a href="https://www.flickr.com/photos/niaid/5149398656" target="_blank">NIAID</a></div></div></div><div class="field field-name-field-image-desctiprion field-type-text field-label-hidden"><div class="field-items"><div class="field-item even">Mycobacterium tuberculosis</div></div></div><div class="field field-name-field-cc-attribute-text field-type-text-long field-label-hidden"><div class="field-items"><div class="field-item even"><p> 探花直播text in this work is licensed under a <a href="http://creativecommons.org/licenses/by-nc-sa/3.0/">Creative Commons Licence</a>. If you use this content on your site please link back to this page. For image rights, please see the credits associated with each individual image.</p>
<p><a href="http://creativecommons.org/licenses/by-nc-sa/3.0/"><img alt="" src="/sites/www.cam.ac.uk/files/80x15.png" style="width: 80px; height: 15px;" /></a></p>
</div></div></div><div class="field field-name-field-show-cc-text field-type-list-boolean field-label-hidden"><div class="field-items"><div class="field-item even">Yes</div></div></div><div class="field field-name-field-license-type field-type-taxonomy-term-reference field-label-above"><div class="field-label">Licence type: </div><div class="field-items"><div class="field-item even"><a href="/taxonomy/imagecredit/attribution">Attribution</a></div></div></div>Mon, 16 Mar 2015 16:00:00 +0000cjb250147832 at Scientists discover genetic disease which causes recurrent respiratory infections
/research/news/scientists-discover-genetic-disease-which-causes-recurrent-respiratory-infections
<div class="field field-name-field-news-image field-type-image field-label-hidden"><div class="field-items"><div class="field-item even"><img class="cam-scale-with-grid" src="/sites/default/files/styles/content-580x288/public/news/news/chestxray2.jpg?itok=2D8ouFHU" alt="X-ray photo of a chest" title="X-ray photo of a chest, Credit: Chikumaya" /></div></div></div><div class="field field-name-body field-type-text-with-summary field-label-hidden"><div class="field-items"><div class="field-item even"><p>Cambridge scientists have discovered a rare genetic disease which predisposes patients to severe respiratory infections and lung damage. Because the scientists also identified how the genetic mutation affects the immune system, they are hopeful that new drugs that are currently undergoing clinical trials to treat leukaemia may also be effective in helping individuals with this debilitating disease.</p>
<p>For the study, led by the 探花直播 of Cambridge in collaboration with the Babraham Institute and the MRC Laboratory for Molecular Biology, the researchers first examined genetic information from individuals who suffer from immunodeficiency and are predisposed to infections. From this group, the scientists identified a unique genetic mutation in 17 patients that suffer from severe respiratory infections and rapidly develop lung damage.</p>
<p> 探花直播researchers, who were primarily funded by the Wellcome Trust, MRC, BBSRC and the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre, found that the mutation increases activity of an enzyme called Phosphoinositide 3-Kinase 未 (PI3K未). 探花直播enzyme is present in immune cells and regulates their function. However, constantly activated PI3K未 impairs work of these immune cells, preventing them from responding efficiently to infection and providing long-lasting protection. Consequently, patients with this mutation have severe and recurrent infections.</p>
<p>鈥淧atients with this mutation have a defect in the immune cells, so their protection from infections is weak and inefficient,鈥� said Sergey Nejentsev, Wellcome Trust Senior Research Fellow from the 探花直播 of Cambridge who led the research. 鈥淲e called this newly identified disease Activated PI3K- 未 Syndrome (APDS) after the enzyme in the immune system that is affected by the genetic mutation.鈥�</p>
<p> 探花直播researchers believe that it may be possible to treat APDS in future. There are currently drugs in clinical trials for leukaemia that were designed specifically to inhibit the PI3K未 enzyme. 探花直播researchers have already shown that these drugs reduce activity of the mutant protein.</p>
<p>Alison Condliffe, joint senior author on the paper from the 探花直播 of Cambridge, said: 鈥淲e are very excited by the prospect of using these drugs to help patients with APDS. We believe that they may be able to restore functions of immune cells, thereby reducing infections and preventing lung damage.鈥�</p>
<p>Although the prevalence of the disease is not yet known, the scientists believe that it is relatively frequent compared to other immunodeficiencies and may underpin immunodeficiencies and chronic lung disorders in a substantial fraction of patients.</p>
<p>鈥淚t is very important that doctors consider a possibility of APDS in their patients,鈥� said Dr Nejentsev. 鈥淎 simple genetic test can tell if the patient has the mutation or not. We believe that now many more APDS patients will be identified all over the world.鈥�</p>
<p> 探花直播research was published by <em>Science</em> Express (the electronic publication of selected <em>Science</em> papers).</p>
</div></div></div><div class="field field-name-field-content-summary field-type-text-with-summary field-label-hidden"><div class="field-items"><div class="field-item even"><p><p>Discovery could lead to new treatments for this genetic disorder.</p>
</p></div></div></div><div class="field field-name-field-content-quote field-type-text-long field-label-hidden"><div class="field-items"><div class="field-item even">We believe that now many more APDS patients will be identified all over the world</div></div></div><div class="field field-name-field-content-quote-name field-type-text field-label-hidden"><div class="field-items"><div class="field-item even">Sergey Nejentsev</div></div></div><div class="field field-name-field-image-credit field-type-link-field field-label-hidden"><div class="field-items"><div class="field-item even"><a href="https://en.wikipedia.org/wiki/File:Chest.jpg" target="_blank">Chikumaya</a></div></div></div><div class="field field-name-field-image-desctiprion field-type-text field-label-hidden"><div class="field-items"><div class="field-item even">X-ray photo of a chest</div></div></div><div class="field field-name-field-cc-attribute-text field-type-text-long field-label-hidden"><div class="field-items"><div class="field-item even"><p><a href="http://creativecommons.org/licenses/by-nc-sa/3.0/"><img alt="" src="/sites/www.cam.ac.uk/files/80x15.png" style="width: 80px; height: 15px;" /></a></p>
<p>This work is licensed under a <a href="http://creativecommons.org/licenses/by-nc-sa/3.0/">Creative Commons Licence</a>. If you use this content on your site please link back to this page.</p>
</div></div></div><div class="field field-name-field-show-cc-text field-type-list-boolean field-label-hidden"><div class="field-items"><div class="field-item even">Yes</div></div></div><div class="field field-name-field-license-type field-type-taxonomy-term-reference field-label-above"><div class="field-label">Licence type: </div><div class="field-items"><div class="field-item even"><a href="/taxonomy/imagecredit/attribution-sharealike">Attribution-ShareAlike</a></div></div></div>Fri, 18 Oct 2013 08:36:28 +0000sj387105962 at New research provides insight into cause of type 1 diabetes
/research/news/new-research-provides-insight-into-cause-of-type-1-diabetes
<div class="field field-name-field-news-image field-type-image field-label-hidden"><div class="field-items"><div class="field-item even"><img class="cam-scale-with-grid" src="/sites/default/files/styles/content-580x288/public/news/research/news/111020-diabetes-jill-a.brown.gif?itok=-7-vY8fv" alt="Diabetes" title="Diabetes, Credit: Jill A. Brown from Flickr" /></div></div></div><div class="field field-name-body field-type-text-with-summary field-label-hidden"><div class="field-items"><div class="field-item even"><p>Everyone carries the IFIH1 gene, which plays a role in the body's antiviral responses. Importantly, it is also located in the region of the human genome associated with T1D, an autoimmune disorder which results in the body attacking its own insulin-producing pancreatic cells. 探花直播IFIH1 gene codes for a protein that recognizes the presence of viruses in the cell and controls immune activation. It is within this gene that scientists have identified four gene variants that protect against T1D.</p>
<p>Enteroviruses are well known to be associated with T1D: enterovirus infections are more common among newly diagnosed T1D patients and pre-diabetic subjects than in the general population and often precede the appearance of biological markers for pre-diabetes. However, no one knows if these infections are a cause of type 1 diabetes.</p>
<p> 探花直播study by Nejentsev et al., which was conducted at the Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, establishes that the IFIH1 protein is involved in T1D, highlighting a molecular pathway by which enterovirus infections may contribute to the development of the disease. 探花直播four rare variants they identified, which are predicted to reduce function of the IFIH1 protein, consistently decrease the risk of T1D, rather than predispose to it. This suggests a model where normal immune activation caused by enterovirus infection and mediated by IFIH1 protein stimulates autoimmunity that eventually leads to T1D.</p>
<p>Professor John Todd, senior author on the study, said: "We have been able to pin-point one particular gene among a long list of candidates. Now we and others can begin to study the biology of IFIH1 in the context of type 1 diabetes knowing that it is part of the cause of the disease."</p>
<p>In the past three years genome-wide association studies have been a major success, revealing dozens of regions in the human genome that harbour genes which predispose individuals to various diseases, such as diabetes or cancers. Nevertheless, as disease-associated regions may contain several genes with different functions, scientists rarely know which gene or gene variant (mutations of the gene) in these regions cause the disease.</p>
<p>In order to overcome this limitation, the scientists searched for variants that had obvious biological effects, e.g. those affecting gene expression or protein function. They hypothesized that if a gene harbors several such variants, then it is likely to be causative. Most of such variants are rare in the population and are not tested in genome-wide association studies. Nevertheless, they could be discovered by sequencing (examining the sequence of the pairs of nucleotides which make up a gene).</p>
<p> 探花直播researchers studied 10 candidate genes associated with T1D. Using a novel technique (high throughput sequencing of DNA pools) in collaboration with 454 Life Sciences, a Roche company, they examined the DNA of 480 T1D patients and 480 healthy controls. This approach allowed them to not only discover several rare variants associated with T1D, but also to accurately measure their frequency in the pools of patients and controls.</p>
<p> 探花直播researchers then genotyped approximately 30,000 individuals who were either T1D patients, controls or family members and proved that four rare variants or versions that reside in the gene IFIH1 reduce the risk of developing T1D.</p>
<p> 探花直播study demonstrates that re-sequencing genes associated with diseases can help pinpoint the specific gene or genes that lead to the disease.</p>
<p>"Finding several new rare disease variants with clear biological functions was crucial. Not only has this proved that IFIH1 is involved in type 1 diabetes, it also gave us clues to understand the mechanism" said Dr. Sergey Nejentsev, Royal Society Research Fellow at the Department of Medicine, the first author of the study. He added: "This experiment shows the way to identify causative genes contributing to various common diseases."</p>
</div></div></div><div class="field field-name-field-content-summary field-type-text-with-summary field-label-hidden"><div class="field-items"><div class="field-item even"><p><p>Scientists from Cambridge 探花直播 have discovered four rare mutations of a gene associated with type 1 diabetes (T1D) that reduce the risk of developing the disease. Their findings, published today in the journal Science, suggest a link between T1D and the enterovirus (a common virus that enters via the gastrointestinal tract but is often non-symptomatic).</p>
</p></div></div></div><div class="field field-name-field-content-quote field-type-text-long field-label-hidden"><div class="field-items"><div class="field-item even">Finding several new rare disease variants with clear biological functions was crucial.</div></div></div><div class="field field-name-field-content-quote-name field-type-text field-label-hidden"><div class="field-items"><div class="field-item even">Dr. Sergey Nejentsev</div></div></div><div class="field field-name-field-image-credit field-type-link-field field-label-hidden"><div class="field-items"><div class="field-item even"><a href="/" target="_blank">Jill A. Brown from Flickr</a></div></div></div><div class="field field-name-field-image-desctiprion field-type-text field-label-hidden"><div class="field-items"><div class="field-item even">Diabetes</div></div></div><div class="field field-name-field-cc-attribute-text field-type-text-long field-label-hidden"><div class="field-items"><div class="field-item even"><p><a href="http://creativecommons.org/licenses/by-nc-sa/3.0/"><img alt="" src="/sites/www.cam.ac.uk/files/80x15.png" style="width: 80px; height: 15px;" /></a></p>
<p>This work is licensed under a <a href="http://creativecommons.org/licenses/by-nc-sa/3.0/">Creative Commons Licence</a>. If you use this content on your site please link back to this page.</p>
</div></div></div><div class="field field-name-field-show-cc-text field-type-list-boolean field-label-hidden"><div class="field-items"><div class="field-item even">Yes</div></div></div>Thu, 05 Mar 2009 00:00:00 +0000bjb4225803 at