Difference between revisions of "Team:BIT"

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    <h2>Preliminary Project Overview</h2>
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<h1> Preliminary project description </h1>
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     <p>Dental caries or  ‘tooth decay’ affects the large majority of the population and even spawned its own field of study, dentistry. As a chronic but non-lethal condition it is often overlooked as a target for modern therapeutics, and its quality of treatment has lagged behind more life-threatening diseases  such as cancer. However, considering how dental caries is a life-long  disease requiring specific self-treatment twice daily as well as  (at minimum!) bi-annual visits  to a specialist - it’s still prevalent. Our team seeks to create a new therapy for dental caries based on  synthetic biology. Hit the road, plaque!</p>
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    <p>The primary bacteria responsible for tooth decay is <i>Streptococcus mutans</i>, a gram-positive microbe that thrives in the salivary microbiome. On teeth it forms biofilms, connected colonies of adherent cells held together by water-insoluble glucans (WIGs) synthesized from ingested sugars. Commonly referred to as dental plaque, this biofilm contains multiple species of <i>Streptococci</i> as well as other microorganisms of the mouth.</p>
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    <p><i>S. mutans</i> release lactic acid as a byproduct of anaerobic respiration, and dense biofilm leads to especially increased extracellular acid because the bacteria have less access to oxygen for aerobic respiration. These high concentrations demineralize teeth and cause cavities to form. Although <i>S. mutans</i> is highly adapted to the biofilm lifestyle, it can also survive in a planktonic form in the mouth. The transition from planktonic to biofilm life is coordinated via quorum sensing.</p>
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Based on the demand of the market and the background, In this project, we design an artificial biological system used for early warning detection a particular biomarkers , we try to use biosensors which will help the cancer screening process become more convenient . Even the LOD(limit of detection) is limited. We will try our best to improve accuracy of this system.  
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    <p>Quorum sensing is a mode of communication employed by many bacteria to coordinate gene expression and behavior across a population or species. Most quorum-sensing systems involve small, diffusible peptides which are sent out as a signal by one bacteria and received by another. After the peptides are detected by a receptor on the cell membrane or in the cytoplasm, the cell initiates a signal transduction pathway that upregulates the quorum-sensing peptide as well as other genes related to the coordinated behavior of the population. Once enough of the signal has been received by the majority of the population, the bacterias’ behavior shifts to perform a synchronized activity.</p>
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The specific method is: to detect the content of specific cancer markers in blood samples by directed engineered bacteria system. Use specific small molecules to replace protein biomarkers’,mostly are macromolecules incoming signal as signal conversion process. After that,small molecules will get into the engineering bacteria, then the bacteria can produce green fluorescent protein through a series of operations.Use microfluidic chip device to load the biological component. And hardware in this system is used to detect the fluorescence signal. After establishing the equivalence relation between fluorescence and biomarkers, biomarkers content in blood will be calculated, and the probability of patients' disease can be deduced. Users can go to the hospital for more accurate detection after receiving early warning information . This is important to the early discovery of the disease in the public, which can reduce the deterioration of the disease due to the lack and late of detection.
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    <p><i>S. mutans</i> employs three quorum-sensing systems: ComRS, LuxR, and ComCDE. Whereas LuxR is a well-defined inter-species signalling system, ComRS and ComCDE are related to biofilms. The ComCDE system is specifically used to initiate biofilm formation through  signalling system involving two steps between the sensing of the small peptide and gene regulation, and is primarily made up of gene products of ComC, ComD, and ComE. The quorum-sensing peptide in this system is known as Competence Stimulating Peptide (CSP), transcribed from the ComC gene. Mature CSP is secreted from the cell using an ABC transporter, a form of efflux pump encoded by the ComA gene. Once outside the cell CSP diffuses into the environment where it can be detected by the ComD receptor kinases on <i>S. mutans</i> cell membranes. CSP is then recognized by the receptor, ComD is autophosphorylated, and its kinase domain has the ability to phosphorylate ComE. This system is known as a two-component signalling system (TCS), and similar signal transduction pathways are present in a wide variety of bacteria.</p>
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    <p>TCS is one of the simplest signal transduction pathways for gene regulation based on external stimuli. It consists of a receptor and a response regulator that binds DNA once its conformation has been changed by the activated receptor.  The response regulator can be an inhibitor or activator and recognizes specific DNA sequences to regulate transcription. <i>S. mutans’</i> response regulator is ComE. It activates the transcription of a variety of genes involved in biofilm formation as well as upregulating genes in the ComCDE system to create a positive feedback loop.</p>
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    <p>For our project, we sought to transplant the sensing functionality of the ComCDE system into mammalian cells. Our goal was to enable human cells to sense CSP and respond with an anti-biofilm agent in order to prevent tooth decay.Our goal is to enable human cells to sense CSP and respond with an anti-biofilm agent in order to prevent tooth decay.  
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Revision as of 13:23, 28 June 2018

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Preliminary project description

Based on the demand of the market and the background, In this project, we design an artificial biological system used for early warning detection a particular biomarkers , we try to use biosensors which will help the cancer screening process become more convenient . Even the LOD(limit of detection) is limited. We will try our best to improve accuracy of this system. The specific method is: to detect the content of specific cancer markers in blood samples by directed engineered bacteria system. Use specific small molecules to replace protein biomarkers’,mostly are macromolecules incoming signal as signal conversion process. After that,small molecules will get into the engineering bacteria, then the bacteria can produce green fluorescent protein through a series of operations.Use microfluidic chip device to load the biological component. And hardware in this system is used to detect the fluorescence signal. After establishing the equivalence relation between fluorescence and biomarkers, biomarkers content in blood will be calculated, and the probability of patients' disease can be deduced. Users can go to the hospital for more accurate detection after receiving early warning information . This is important to the early discovery of the disease in the public, which can reduce the deterioration of the disease due to the lack and late of detection.