Team:UCL/Project/Developments

From 2013.igem.org

(Difference between revisions)
Line 49: Line 49:
<p class="major_title">OTHER PARTS OF OUR CIRCUIT</p>
<p class="major_title">OTHER PARTS OF OUR CIRCUIT</p>
<p class="minor_title">Avoiding Inflammation And Supporting Neurons</p>
<p class="minor_title">Avoiding Inflammation And Supporting Neurons</p>
 +
<div class="gap">
 +
</div>
<p class="body_text">
<p class="body_text">
-
Lorem ipsum dolor sit amet, consectetur adipiscing elit. Vivamus vel fringilla diam. Integer placerat sapien sed risus mollis, eget hendrerit lorem tincidunt. Cras a sem eros. Ut nec ligula eget tortor ornare tempus sit amet quis risus. Quisque condimentum, ipsum ac rhoncus ornare, tellus augue imperdiet libero, in venenatis justo arcu quis tellus. Vivamus magna libero, tempus ac augue at, placerat vulputate nunc. Praesent fringilla id erat ut sagittis. Sed nec semper risus, nec condimentum leo. Vestibulum pharetra pellentesque augue, non ultrices leo varius et. Vestibulum id egestas orci. Vestibulum metus ipsum, iaculis nec sapien in, fringilla cursus orci. Class aptent taciti sociosqu ad litora torquent per conubia nostra, per inceptos himenaeos. Curabitur eget vulputate ligula. Sed venenatis nulla et porta pharetra. Suspendisse pharetra suscipit justo sagittis consequat. Morbi eu iaculis diam, ac rhoncus urna. Pellentesque eros ligula, mollis vitae metus sit amet, interdum gravida nunc. Duis tempor quam id rhoncus sodales. Nunc commodo accumsan orci ut faucibus. Quisque vitae luctus libero. Nullam risus libero, convallis et viverra sit amet, convallis a neque. Integer adipiscing ac arcu sit amet luctus. In dignissim mauris non justo tempor, in rhoncus augue volutpat. Duis euismod sodales blandit. Vivamus volutpat molestie dignissim. Quisque cursus quam cursus dui faucibus convallis. Praesent dignissim, sem ut posuere accumsan, libero diam consequat libero, vel tempor dui mi sed massa. Aenean eros arcu, sollicitudin a euismod eu, placerat vel nunc. Nunc consequat blandit fermentum. Curabitur ante erat, lobortis ac faucibus a, sollicitudin egestas nisi. Morbi ut dolor scelerisque, fermentum est vitae, commodo tortor. Vestibulum ornare semper lorem vel volutpat. In erat ligula, auctor eu pellentesque vitae, sollicitudin id sapien. Duis pharetra sagittis purus hendrerit pharetra. Lorem ipsum dolor sit amet, consectetur adipiscing elit. Vivamus elementum iaculis neque nec fringilla. Nunc a scelerisque nulla, et varius massa. In eu pretium eros. Quisque nec lacus elit. Mauris malesuada luctus dapibus. Vivamus eget ultricies sem. Quisque nulla tellus, euismod vel vehicula adipiscing, ornare sit amet dui. Sed eget mauris aliquam, feugiat diam vel, lacinia nunc. Ut vel est facilisis, dictum sem sit amet, lobortis arcu. In hac habitasse platea dictumst. Fusce ut accumsan sapien. Sed pharetra ullamcorper dolor vitae rutrum. Aliquam luctus mattis felis vitae semper. Vivamus id sodales purus. Cras quis quam non tortor tincidunt laoreet varius suscipit lectus. Curabitur faucibus et libero quis vulputate. Nunc sed gravida libero. Phasellus eleifend, metus mattis molestie luctus, augue libero lacinia massa, ac volutpat tortor tortor quis sapien. Donec ultrices felis ut arcu rutrum sollicitudin. Praesent nec ligula at risus hendrerit aliquam. Etiam vestibulum aliquam ultricies. Ut semper libero volutpat, rutrum enim et, eleifend nibh. Nulla ornare, elit sed laoreet condimentum, quam nunc auctor sem, eu commodo elit ante id magna.  
+
Unfortunately, we did not have time to attempt to create all the parts envisioned in our original potential. However, we believe that they are theoretically significant, and so here we explain what more could be done to improve this project of ours, as we work on these improvements after the ‘WikiFreeze’ for the Regional Jamboree of the iGEM competition.  
 +
</p>
 +
<p class="body_text">
 +
The strength of our system [internal link to circuit overview] is that the microglial chassis [internal link to microglia page in background] already detect and engage [internal link to chassis page] amyloid plaques [internal link to neuropathology].
 +
</p>
 +
<p class="body_text">
 +
This means that our systems can create proteins in situ to improve the Alzheimer’s disease [link to Alzheimer’s disease in background] state. However, amyloid proteases such as MMP-9 [internal link to ‘degradation’] would only have a positive impact on the pathology if the ‘Amyloid Hypothesis’ [internal link to neuropathology] is correct, and there is some evidence to suggest that it may not be.  
 +
</p>
 +
<p class="body_text">
 +
It is thought that Alzheimer’s disease (AD) may be exacerbated into a neurodegenerative condition by the action of microglia themselves, the custodians of the brain. They can inflame the plaque area, and this damages neurons. Therefore, we propose producing a de-activating agent, such as vasoactive intestinal peptide (VIP), BioBrick with an oxidative stress promoter [internal link to detection]. This mean that our engineered microglia would activate when it detects a plaque and move towards that plaque. As it approaches, oxidative stress increases so that once near the plaque the de-activating agent would return the engineered cell and wild-type cells surrounding the plaque into their resting state, avoiding neuroinflammation. This would stop them from producing amyloid proteases such as neprilysin. However, our MMP-9 BioBrick can ensure that amyloid degradation continues (the positive action of microglia in AD) without inflammation (the negative action of microglia in AD).  
 +
</p>
 +
<p class="body_text">
 +
It is also thought that AD may initiate due to cell-cycle re-entry on account of a disbalance in neurotrophin signalling [internal link to neuropathology]. Brain-derived neurotrophic factor (BDNF) is a signal that sustains neurons. If expressed by engineered microglia at plaque localities it could support dying neurons and stop other neurons progressing into an AD state.  
</p>
</p>
<div class="gap"></div>
<div class="gap"></div>

Revision as of 14:09, 5 September 2013

OTHER PARTS OF OUR CIRCUIT

Avoiding Inflammation And Supporting Neurons

Unfortunately, we did not have time to attempt to create all the parts envisioned in our original potential. However, we believe that they are theoretically significant, and so here we explain what more could be done to improve this project of ours, as we work on these improvements after the ‘WikiFreeze’ for the Regional Jamboree of the iGEM competition.

The strength of our system [internal link to circuit overview] is that the microglial chassis [internal link to microglia page in background] already detect and engage [internal link to chassis page] amyloid plaques [internal link to neuropathology].

This means that our systems can create proteins in situ to improve the Alzheimer’s disease [link to Alzheimer’s disease in background] state. However, amyloid proteases such as MMP-9 [internal link to ‘degradation’] would only have a positive impact on the pathology if the ‘Amyloid Hypothesis’ [internal link to neuropathology] is correct, and there is some evidence to suggest that it may not be.

It is thought that Alzheimer’s disease (AD) may be exacerbated into a neurodegenerative condition by the action of microglia themselves, the custodians of the brain. They can inflame the plaque area, and this damages neurons. Therefore, we propose producing a de-activating agent, such as vasoactive intestinal peptide (VIP), BioBrick with an oxidative stress promoter [internal link to detection]. This mean that our engineered microglia would activate when it detects a plaque and move towards that plaque. As it approaches, oxidative stress increases so that once near the plaque the de-activating agent would return the engineered cell and wild-type cells surrounding the plaque into their resting state, avoiding neuroinflammation. This would stop them from producing amyloid proteases such as neprilysin. However, our MMP-9 BioBrick can ensure that amyloid degradation continues (the positive action of microglia in AD) without inflammation (the negative action of microglia in AD).

It is also thought that AD may initiate due to cell-cycle re-entry on account of a disbalance in neurotrophin signalling [internal link to neuropathology]. Brain-derived neurotrophic factor (BDNF) is a signal that sustains neurons. If expressed by engineered microglia at plaque localities it could support dying neurons and stop other neurons progressing into an AD state.