Team:UCL/Project

From 2013.igem.org

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Revision as of 14:24, 4 September 2013

INTELLIGENTLY GENETICALLY ENGINEERED MICROGLIA

Synthetic Biology Fights Alzheimer's Disease

This year, the UCL iGEM team is taking a radical new step with synthetic biology. We intend to explore the potential application genetic engineering techniques on the brain, because it is the site of some of the most subtle, and many of the most devastating medical conditions. Alzheimer’s Disease is a neurodegenerative disease characterised by the loss of recent memory and intellectual functions. We have devised a genetic circuit for transfection into microglia, a novel chassis in which standard assembly has never been used, to boost their ability to break down senile plaques, which are associated with Alzheimer’s disease, as well as to support and protect endangered neurons from microglia-mediated neuroinflammation.

Click the abstracts below to read more.

Circuit Overview

Our genetic circuit aims primarily to remove amyloid plaques in the brain, which are associated with Alzheimer’s disease, prevent neuroinflammation and support neurons.

Detection

Senile plaques increase the rate of production of reactive oxygen species that are damaging to brain cells. We developed an oxidative stress promoter, in order to initiate the production of other circuit parts.

Chemotaxis

Microglia readily migrate towards plaques in vivo, but to see if we could increase migration to plaques, we produced a chemoattractant to help them converge.

Degradation

We expressed and characterised a matrix metalloproteinase that is capable of degrading amyloid. By increasing its expression in de-activated microglia, we hope to reduce amyloid burden in Alzheimer’s disease.

Selectable Marker

We used resistance to zeocin, a cell killing glycoprotein, to act as a selectable marker for transformation/transfection in our chassis; E.coli, HeLa and microglia.

Chassis

We conducted our experiments in three chassis, creating recombinant plasmids in E.coli before expressing them in HeLa and finally primary and immortalised human microglia lines.

Parts

We submitted X parts to the registry, LIST GENE NAMES and improved X, LIST GENE NAMES. To be filled in later

Future Developments

Our circuit design is far from finished; given sufficient time in the lab, we would have included several other important components, including the de-activating agent VIP and the support factor BDNF.

Experiments

Fill in later.

Lab Protocols

Fill in later.

Safety

It is essential that both personnel and experimental products are as safe as possible to avoid harm. Risk may be minimised by following safety procedures for any plausible dangerous situation that may occur in the laboratory.

Retrieved from "http://2013.igem.org/Team:UCL/Project"