Difference between revisions of "Team:MIT/Diagnosis and Future Implications"

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    <a href="https://2016.igem.org/Team:MIT/Experiments/Promoters">
 
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      <img src="https://static.igem.org/mediawiki/2016/0/0c/T--MIT--ImagePannel_promoter.png" alt="Promoter">
 
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      <span class="text-content"><span>Hormones Responsive Promoters</span></span>
 
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    <a href="https://2016.igem.org/Team:MIT/Experiments/miRNA">
 
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      <span class="text-content"><span>miRNA Profile</span></span>
 
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    <a href="https://2016.igem.org/Team:MIT/Experiments/Recombinases">
 
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      <span class="text-content"><span>Recombinase Biological Latch</span></span>
 
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<h1 style="color:#000000; background-color:#7ecefd;; -moz-border-radius: 15px; -webkit-border-radius: 15px; padding:15px; text-align: center; font-family: Trebuchet MS"> How does endometriosis respond to the menstrual cycle?</h1>   
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<h1 style="color:#000000; background-color:#7ecefd;; -moz-border-radius: 15px; -webkit-border-radius: 15px; padding:15px; text-align: center; font-family: Trebuchet MS"> Developing a diagnosis</h1>   
  
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<p style="font-family: Verdana; float:left;"> Endometriosis cells respond to the hormones associated with the menstrual cycle. Interestingly, the miRNA profile of these cells is different during the proliferative versus the secretory phase. TALK MORE ABOUT THIS STUFF. I DON’T KNOW ANYTHING :(  </p>
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<p style="font-family: Verdana; float:left;"> Endometriosis is a complex disease – any diagnostic needs to account for a variety of factors. We opted for a three-pronged approach, sensing progesterone resistance and miRNA dysfunction while maintaining temporal specificity. Each of these components represents a key hallmark of the disease, and when put together can create a sensitive diagnostic tool. </p>
  
 
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<h1 style="color:#000000; background-color: #7ecefd;; -moz-border-radius: 15px; -webkit-border-radius: 15px; padding:15px; text-align: center; font-family: Trebuchet MS"> How can our circuit demonstrate temporal specificity?</h1>   
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<h1 style="color:#000000; background-color: #7ecefd;; -moz-border-radius: 15px; -webkit-border-radius: 15px; padding:15px; text-align: center; font-family: Trebuchet MS"> A Proposed Genetic Circuit </h1>   
  
 
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Endometriosis cells have distinct characteristics at different points in the menstrual cycle, presenting a major challenge in identifying diseased cells. It is crucial that there is a way to achieve temporal specificity.
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There should be a circuit diagram or flow-chart here, along with an explanation of how it works.
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Recombinases are enzymes that can recognize target sequences, and depending on their orientation, can either cut out DNA between the recognition sites or invert the DNA sequence. There are two main families of recombinases - serine recombinases (also sometimes called serine integrases) and tyrosine recombinases. Serine integrases invert sequences while tyrosine recombinases can either cut or flip sequences depending on the orientation of recognition sites. Some recombinases exhibit unidirectionality, meaning once they reverse or cut the sequence the action cannot be undone. This means that instead of behaving like a switch, capable of turning on or off, unidirectional recombinases behave as latches.
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We can use recombinases as biological latches in our circuit to gain temporal specificity.  Once a cell is identified as having the miRNA profile characteristic of a diseased cell, a recombinase can be activated to essentially “lock in” that information. When the second half of the circuit confirms the cell as being diseased, a second recombinase latch can be triggered, activating the overall circuit.  
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<h1 style="color:#000000; background-color: #7ecefd;; -moz-border-radius: 15px; -webkit-border-radius: 15px; padding:15px; text-align: center; font-family: Trebuchet MS"> Do our recombinases work?</h1>
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<h1 style="color:#000000; background-color: #7ecefd;; -moz-border-radius: 15px; -webkit-border-radius: 15px; padding:15px; text-align: center; font-family: Trebuchet MS"> Implementing a Diagnosis </h1>
  
 
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We used the serine integrase TP901 to flip an inverted eYFP... talk more about this.
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We initially contemplated creating an in-vivo diagnostic, but changed our minds after speaking with Professor Linda Griffith (MIT). Realistically, inserting a genetic circuit into a human (likely through the use of a viral vector) is many years away from being a possibility due to major safety concerns. Implementing an in-vitro diagnostic that can be used on an endometrial biopsy is more feasible. An endometrial biopsy is a procedure that can be done in a doctor’s office without anesthesia and is commonly used when testing for endometrial cancer. While not a pain-free procedure, endometrial biopsies are considerably less invasive than laparoscopic surgery, the current diagnostic method for endometriosis. The tissue from the biopsy can be dosed with hormones.... TALK MORE ABOUT THIS, UNSURE OF SPECIFICS.
 
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    <a href="https://2016.igem.org/Team:MIT/Experiments/EGSH_TP901_Experiment"><p style="font-family: Trebuchet MS;font-color:#7ECEFD"><i>Read more about recombinases experiments here</i></p></a>
 
  
 
      
 
      
 
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<h1 style="color:#000000; background-color: #7ecefd;; -moz-border-radius: 15px; -webkit-border-radius: 15px; padding:15px; text-align: center; font-family: Trebuchet MS"> Challenges with Recombinases</h1>   
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<h1 style="color:#000000; background-color: #7ecefd;; -moz-border-radius: 15px; -webkit-border-radius: 15px; padding:15px; text-align: center; font-family: Trebuchet MS"> Synthetic Biology & Medicine - How SynBio Approaches Can Transform Diagnostics </h1>   
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Recombinases are highly efficient enzymes. When combined with a high basal level of activity, this presents a challenge. In order for the effective use of recombinases as biological latches, basal expression must be reduced as much as possible. A strong repression system must be used in order to reduce leaky expression.
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Our approach of using a genetic circuit to sense diseased cells presents possibilities beyond endometriosis. Similar strategies can be used to diagnose other diseases... KEEP GOING WITH THIS
 
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<h2 style="text-decoration:underline; font-family: Trebuchet MS;"> Repressible Promoters</h2>
 
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<h2 style="text-decoration:underline; font-family: Trebuchet MS;"> Translational Regulation: L7Ae - kink turn</h2>
 
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    <a href="https://2016.igem.org/Team:MIT/L7AeRepressingSystem"><p style="font-family: Trebuchet MS;font-color:#7ECEFD"><i>Read more about our L7Ae k-turn experiment here</i></p> </a>
 
 
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Revision as of 02:25, 15 October 2016

Diagnosis and Future Implications

Developing a diagnosis

Endometriosis is a complex disease – any diagnostic needs to account for a variety of factors. We opted for a three-pronged approach, sensing progesterone resistance and miRNA dysfunction while maintaining temporal specificity. Each of these components represents a key hallmark of the disease, and when put together can create a sensitive diagnostic tool.

A Proposed Genetic Circuit

There should be a circuit diagram or flow-chart here, along with an explanation of how it works.

Implementing a Diagnosis

We initially contemplated creating an in-vivo diagnostic, but changed our minds after speaking with Professor Linda Griffith (MIT). Realistically, inserting a genetic circuit into a human (likely through the use of a viral vector) is many years away from being a possibility due to major safety concerns. Implementing an in-vitro diagnostic that can be used on an endometrial biopsy is more feasible. An endometrial biopsy is a procedure that can be done in a doctor’s office without anesthesia and is commonly used when testing for endometrial cancer. While not a pain-free procedure, endometrial biopsies are considerably less invasive than laparoscopic surgery, the current diagnostic method for endometriosis. The tissue from the biopsy can be dosed with hormones.... TALK MORE ABOUT THIS, UNSURE OF SPECIFICS.

Synthetic Biology & Medicine - How SynBio Approaches Can Transform Diagnostics

Our approach of using a genetic circuit to sense diseased cells presents possibilities beyond endometriosis. Similar strategies can be used to diagnose other diseases... KEEP GOING WITH THIS