Team:UCL/Notebook

From 2013.igem.org

(Difference between revisions)
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We need to register this part!
We need to register this part!
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</p>
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<p class="minor_title">13th June</p>
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Alex sent the 3 main project proposals to Dr. Darren Nesbeth for review.
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</p>
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Tom and Andy edited the wiki page adding various sections and elaborating on previously created pages.
 +
</p>
 +
Weiling researched on killing mechanisms being able to target hypoxic regions of solid tumors and promoters in hypoxia environments.
 +
</p>
 +
Catrin - General project research
 +
</p>
 +
Ruxi - Further researched the potential promoters esp HIP 1 and the Fas regulated programmed apoptosis.
 +
</p>
 +
We attended a Synthetic Biology talk by Neil Dixon, University of Manchester (Tom and Andy).
 +
</p>
 +
Had a general meeting for discussion of what has been accomplished so far, and the subsequent actions, which are to be undertaken by team members. Further documents were also submitted to Dr. Darren Nesbeth concerning 'team roles'. The team then began to do individual research or other activity:
 +
</p>
 +
Tom and Robin - Edited the iGEM wiki, added team information and removed the unnecessary tutorial information, replacing it with more useful information and streamlining the whole interface.
 +
</p>
 +
Weiling and Alex - Further development of circuit ideas, taking inspiration from previous iGEM ideas as well as further research into the CD95L molecule.
 +
</p>
 +
Ruxi and Catrin - Research into latching molecules for a bacteria to tumour interface to increase target specificity. Idea encounted from Hong Kong 2012 where Colon Cancer was targeted.
</p>
</p>
 +
 +
<p class="minor_title">14th June</p>
 +
Tom - Website design for: Main Page, UCL information, Team based pages and Notebook pages
 +
</p>
 +
Robin - Coding in HTML for website
 +
</p>
 +
Ruxi, Caitlin, Weiling - Further investigation of Hong Kong 2010 to see what parts may be improved or of use to the project, these were: a blue light activated promoter, how can the quorum sensing and CagA be exploited, a negative regulatory system for drug secretion.
 +
</p>
 +
Alex - searched for potential bacterial receptor to be modified in order to be a good target for something else in the environment/cancer cell surface.
 +
</p>
 +
<p class="minor_title">17th June</p>
 +
 +
The group had a meeting to discuss what had been achieved so far and what needed to be done today.
 +
</p>
 +
Tom - Continued on website design and wrote several pieces concerning UCL to be used on the website when it goes live.
 +
</p>
 +
Robin - Continued on website coding.
 +
</p>
 +
Weiling & Catrin - Researched for project sponsors and potential contacts.
 +
</p>
 +
Alex, Ruxi, StJohn & Andy - Continued research into the project ideas.
 +
</p>
 +
</div>
</div>

Revision as of 11:18, 5 September 2013

January

First meeting was held after the team had been assembled. Introductions to each other and team building exercises take place to familiarise to help everyone get to know each other. Discussions take place with previous iGEM team members from UCL so the new team gain some context and guidance concerning how to approach an iGEM project.

Each member of the new team was told to present for 5 minutes on a 2012 based team, commenting on their strengths and weaknesses. Further discussions about the general area 'track' that the team would be interested in. Given that many team members have a medical sciences background, medical based ideas were favoured among the majority of the team.

February

First meeting was held after the team has been assembled. Introduction to each other and team building exercises take place to familiarise the team members with each other. Discussions take place with previous iGEM team members from UCL so the new team have some context and guidance concerning how to approach any iGEM project.

• Weight control yoghurt

• Anti-cancer yoghurt

• Zebrafish water cleaning system for Third World

• Athletic Drug testing

• Clean Urban Air

• Neural network with glowing bacteria and fibre optics

Visited a DIY SynBio group at The Arts Catalyst for feedback on our project ideas and to display posters we can created for them, in order to get feedback from the members of the public who came to the venuw for synbio workshops. Some of the members there were previous iGEM candidates from several countries, with many liking the anti cancer yoghurt idea. In general, the publlic found medical projects more appealing, partly becuase they tried to solve tangible problems that cannot be mitigated soley by 'electrical' or 'mechnaical' technologies. The 'neural networks' idea gathers interest with scientists at Cancer Reserach UK and members of the public alike becuase bringing apllying synethtic biology to study neuroscience seems both innovative and relatively original. The zebrafish idea gathers interest becuase of the novel chassis. The other ideas do not do so well due to commonly being seen in iGEM, and being common promises of synthetic biology in general.

March

Final meetings before exams, both internally and at the Arts Catalyst. In the mean time we had taken on board our feedback, and took the best ideas from each of the most popular project to come up with a new idea that combined takling a medical condition, with neuroscience, with using a novel chassis in an Alzheimer's disease project. The idea pool has now been narrowed down to:

• Anti-cancer yoghurt

• Zebrafish

• Alzheimer's disease

• Neural Network

Members of the group also held a probiotic yoghurt workshop for the anti-cancer project, where members of the public made yoghurt. The audience were informed about the project and opinions were gathered. Again, the fact that the porject was medical was well received, though some ethical concerns were raised so that we knew we would have to make bioethics a big part of our project from the start.

April & May

Exam period - iGEM work to commence full time after the slog through exams.

June

5th June

Group discussion concerning the project idea to be carried forward - favouring the 'Anti cancer project'. Roles were then assigned to team members present for intial research roles for the week:

Cancer research roles:

1. Ruxi Comisel - Proteins upregulated in cancer of the intestines. Specifically in the outer epithelial cell (enterocytes) – in microvilli. Also, what actually is... gut cancer? A general overview would be useful…

2. Khaicheng Kiew - Our chassis (bearing in mind that we will also build it in E. coli as a backup). We need to think what would make a good chassis in our case (ie. naturally found in the gut in an obvious one), and how well does the chassis fit.

3. Alex Bates - What will the killing mechanism be? A broad overview of cancer treatments is required, specifically detailing how a bacterium can administer the treatment.

Considerations:

a. The bacteria may secrete a toxin etc – how will we ensure that it doesn’t simply diffuse through the gut? b. If it is a toxin, what sort of biosynthetic pathway is required? c. Does the bacteria trigger apoptosis in the cancer cells (ie. an intracellular killing mechanism)? How can this be done from an extracellular bacterium? Perhaps beta-arrestin? d. Are there any treatments which we can take advantage of specifically because we are using bacteria? e. For example, a protein which creates holes in the cancer cells? Does using a bacterium open up the possibility of using a different cure that currently isn’t in use because we cannot target it to cancer cells – could the use of bacteria allow this?

4. Weiling Yuan - Targeting – do we use antibodies? What previous projects have used bacteria expressing antibodies? Are there any other ways of doing this? Perhaps the latching and initiation mechanisms can be incorporated into one protein?

5. StJohn Townsend - Initiation – mechanoreceptor activated upon latching? What other ways are there of doing this?

6. Tom Johnson - Past iGEM projects which we could incorporate into our own: Cancer projects, Gut projects, Protein engineering, Antibodies expressed in bacteria etc.

7th June

The team discusses findings from the initial research - further agreement that the 'Anti Cancer' project seemed to be the best idea, preparation of 'project sheets' to be sent to Dr. Darren Nesbeth for review and subsequent meetings.

11th June

looked a bit at the possible chassis species: salmonella, clostridium, helicobacter, E. coli. according to the tissue type/cancer type we shall decide which works with which. We start with E. coli in the lab.

We considered a pro-drug approach - bacterially directed enzyme pro-drug therapy which suggests that we may establish a transformed bacterial population with an enzyme capable to activate an ingested prodrug. This pro-drug would be connected to an antibody (possibly part of the tail) and would also have linking consensus sequence targeted by the enzyme produced locally by our bacteria.

From this above point Alex distinguished 2 scenarios built on the circuit sketch that he and Laia posted a while ago. These would be:

1) Kill unit produces tailed protein pro-drug (possibly tailed perforin) and signaling molecule, A. When A reaches a threshold amount, perforin and a protease to remove the confounding tail is produced, bacteria lyses and activated pro-drug acts on surrounding cells.

2) No protease is produced, because the tail can be cleaved off by matrix metalloproteases.

Goals for the end of this week:

- Alex, Andy and Weiling continue investigating possible candidates to fill in the parts for the scenarios

-Tom, KC and Ruxi make sure we have everything set up to start the work in the lab: protocol, parts etc.

12th June

Ruxi and Tom went through a general cloning protocol but then realised that the best way to prepare for the lab is to get familiarised with the iGEM distribution kits. We discovered that we are given almost everything we need in order to get it right.

Alex filled in the form with our proposal requested by Darren - we have the sequences and details of potential new biobricks.

We formulated a new proposal regarding the Alzheimer’s disease amyloid plaque degradation.

Andy searched potential cancer killer molecules:

- CD95 - Fas agonist (http://www.nature.com/cdd/journal/v14/n4/full/4402051a.html) - Tumor Necrosis Factor, Histamine - induces inflammation - HAMLET (human a-lactalbumin) - induces apoptosis - endostatin, thrombospondin - reduce cancer growth

Weiling looked at potential promotors:

- RacA (based on increased DNA damaged due to radiation) to start the killing cascade and CD95 as a potential killer molecule - Lux pR promotor - Lld promoter - Vgb promotor - HIP-1

(about gastric Oxygen levels: http://www.biomedcentral.com/1471-2180/11/96)

For promoter 1 (switches on the pro-drug and signaling molecule transcription), a very good candidate is HIP 1 promoter - hypoxia-inducible promoter which drives reporter gene expression under both acute and chronic hypoxia. It was developed in attenuated Salmonella species. Take a look here: 　 http://www.landesbioscience.com/journals/cbt/article/2951/mengesha5-9.pdf

We need to register this part!

13th June

Alex sent the 3 main project proposals to Dr. Darren Nesbeth for review.

Tom and Andy edited the wiki page adding various sections and elaborating on previously created pages.

Weiling researched on killing mechanisms being able to target hypoxic regions of solid tumors and promoters in hypoxia environments.

Catrin - General project research

Ruxi - Further researched the potential promoters esp HIP 1 and the Fas regulated programmed apoptosis.

We attended a Synthetic Biology talk by Neil Dixon, University of Manchester (Tom and Andy).

Had a general meeting for discussion of what has been accomplished so far, and the subsequent actions, which are to be undertaken by team members. Further documents were also submitted to Dr. Darren Nesbeth concerning 'team roles'. The team then began to do individual research or other activity:

Tom and Robin - Edited the iGEM wiki, added team information and removed the unnecessary tutorial information, replacing it with more useful information and streamlining the whole interface.

Weiling and Alex - Further development of circuit ideas, taking inspiration from previous iGEM ideas as well as further research into the CD95L molecule.

Ruxi and Catrin - Research into latching molecules for a bacteria to tumour interface to increase target specificity. Idea encounted from Hong Kong 2012 where Colon Cancer was targeted.

14th June

Tom - Website design for: Main Page, UCL information, Team based pages and Notebook pages

Robin - Coding in HTML for website

Ruxi, Caitlin, Weiling - Further investigation of Hong Kong 2010 to see what parts may be improved or of use to the project, these were: a blue light activated promoter, how can the quorum sensing and CagA be exploited, a negative regulatory system for drug secretion.

Alex - searched for potential bacterial receptor to be modified in order to be a good target for something else in the environment/cancer cell surface.

17th June

The group had a meeting to discuss what had been achieved so far and what needed to be done today.

Tom - Continued on website design and wrote several pieces concerning UCL to be used on the website when it goes live.

Robin - Continued on website coding.

Weiling & Catrin - Researched for project sponsors and potential contacts.

Alex, Ruxi, StJohn & Andy - Continued research into the project ideas.

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