Difference between revisions of "Team:Oxford"

Line 160: Line 160:
 
         <div class="row">
 
         <div class="row">
 
           <div class=".col-md-8 .offset-md-2">
 
           <div class=".col-md-8 .offset-md-2">
−
             <h2>Project overview<br></h2>
+
             <h2>Abstract<br></h2>
−
             <p class="lead"><br>We are engineering gut bacteria to treat IBD. We have created a system to accurately determine and control the balance of immune cells in the gut. Our device detects the proportion of populations of Th17 cells and Treg cells and produces specific amounts of an immune suppressor to prevent an autoimmune and an immunodeficient state. <br><br>The device will detect NO (representative of Th17 population) and respond by producing a relevant amount of IL-10. IL-10 promotes Treg population growth and inhibits Th17 population growth. NO will be detected by a SoxR/pSoxS system. To prevent the population of Treg cells becoming too large, and creating an immunodeficient state, we have created a mechanism to detect and respond to Treg population growth. Adenosine is representative of Treg cell populations. <br><br>We are adding a cytoplasmic-excluded hydrolase to the outside of the cell to break down adenosine to adenine. Adenine will activate a riboswitch which will allow an sRNA to be transcribed, binding to IL-10 mRNA preventing IL-10 from being translated and so acting as an off switch. </p>
+
             <p class="lead"><br>Inflammatory Bowel Disease (IBD) is characterised by chronic inflammation of the intestine. The condition is associated with an imbalance in immune cell populations, notably Th17 and Treg. Existing immunosuppressive therapies, when successful, often elicit systemic side effects and require frequent readministration. Our solution is to develop a probiotic strain that restores the Th17/Treg cell balance via secretion of IL-10 in response to nitric oxide in the intestinal lumen. Overshoot is prevented by an adenine riboswitch-sRNA construct which responds to extracellular adenosine, an indicator of the Treg cell population. Integration of separate stimuli in a dual feedback loop enables a more dynamic, robust response to the immune state of the body. Various features have been incorporated to maximise biological safety, including an inducible kill switch system. We believe our design offers a non-invasive, self-tuning therapeutic for IBD, with potential to replace conventional immunosuppressants in the treatment of gastrointestinal autoimmune disorders. </p>
  
 
           </div>
 
           </div>
Line 172: Line 172:
 
         <div class="row">
 
         <div class="row">
 
           <div class=".col-md-8 .offset-md-2 .bg-light">
 
           <div class=".col-md-8 .offset-md-2 .bg-light">
−
            <h2>Autoimmune diseases<br></h2>
 
−
            <p class="lead"><br>Autoimmune disease are a range of disorders that result from attack of self-tissues by a dysregulated immune system. Examples are multiple sclerosis, Crohn's disease and type I diabetes. There are significant global inequalities in the treatment and prevalence of autoimmune disorders. 80% of diagnoses of autoimmune epilepsy are in the developing world. This is caused by the production of antibodies against proteins in the brain such as GABA receptors. However, it should be noted that prevalence of autoimmune diseases is greater in Europe and the USA. This is explained by the hygiene hypothesis which suggests that a lack of exposure to microorganisms, both pathogenic and symbiotic, prevents normal development of the immune system.
 
−
 
−
<br><br>T helper (Th) cells produce immune responses and T regulatory (Treg) cells control the populations of Th cells. When Treg cell populations are low they are unable to stop excessive growth of helper cell populations. Th cells will produce superfluous inflammatory molecules that spread. This is the cellular basis of autoimmune disease.
 
−
 
−
<br><br>We have focused on autoimmune diseases in developing countries where bacteria, such as segmented filamentous bacteria (SFB) are prevalent and typically found within water sources. SFB are gram positive bacteria that are tightly bound to the lining of the gut epithelia and have recently been implicated in modifying host immune responses by promoting the development of lymphocytes and the growth of Th17 populations. An additional effect of the signals required for Th17 differentiation is the inhibition of the production of Treg cells. Once fully differentiated, Th17 cells produce interleukin 17a (IL-17a) a proinflammatory cytokine. Elevated levels of IL-17a are associated with MS and the development of epilepsy and other autoimmune diseases.
 
−
</p>
 
 
           </div>
 
           </div>
 
         </div>
 
         </div>

Revision as of 11:45, 13 October 2018

Full Width Pics - Start Bootstrap Template
1 / 3
Google
2 / 3
Meet the Team
3 / 3
Caption Three

Abstract


Inflammatory Bowel Disease (IBD) is characterised by chronic inflammation of the intestine. The condition is associated with an imbalance in immune cell populations, notably Th17 and Treg. Existing immunosuppressive therapies, when successful, often elicit systemic side effects and require frequent readministration. Our solution is to develop a probiotic strain that restores the Th17/Treg cell balance via secretion of IL-10 in response to nitric oxide in the intestinal lumen. Overshoot is prevented by an adenine riboswitch-sRNA construct which responds to extracellular adenosine, an indicator of the Treg cell population. Integration of separate stimuli in a dual feedback loop enables a more dynamic, robust response to the immune state of the body. Various features have been incorporated to maximise biological safety, including an inducible kill switch system. We believe our design offers a non-invasive, self-tuning therapeutic for IBD, with potential to replace conventional immunosuppressants in the treatment of gastrointestinal autoimmune disorders.