"

From 2014.igem.org

Initial Brainstorm Ideas

• A biosensor for a world wide disease

• Detecting PAMPs in bacterial by a novel cleavage mechanism in simulated serum samples

* Detecting pneumolysin for strep. pneumo by using specific antigens/receptors

IDEA #1

PAMPS are referred to as pathogen associated molecular patterns, they're basically parts of bacteria that are recognized by our immune system as foreign. I've followed up and researched a bit more about this idea and propose that we could possibly:

Introduce a number of genes into a particular cell line, since each of our cells have specific proteins called caspases that are cleaved upon detecting a bacterial product (e.g Flagellin from bacteria); these caspases normally cause a number of processes that leads to cell death but ONLY upon sensing bacterial products, they become active. However, if we could somehow get caspases to recognize a particular protein (e.g green florescent protein - GFP) into our introduced samples and cleave it so that GFP becomes active, then we've developed a cool biological sensor that can detect particular bacterial products. Of course, similarly we'd have to make sure that we prevent cell death from occurring (this could be through the introduction of inhibitors of effector caspases e.g Caspase 3 that are the actual executors of cell death.)

Below I've attached a review on caspases https://yuan.med.harvard.edu/sites/yuan.med.harvard.edu/files/documents/onc2008297a.pdf

An insightful page on GFP (note there's also other different colours e.g YFP, RFP that could also be introduced as well - so that if we introduce other different bacterial products, e.g instead of flagellin something else like LPS than it would florescence a different color)

http://www.conncoll.edu/ccacad/zimmer/GFP-ww/shimomura.html

I've also attached a paper that demonstrates the feasibility of this approach (at least in recognition and cleavage of a fluorescent protein) in this paper they basically were able to engineer a GFP that can be cleaved by caspases and becomes active.

http://www.ncbi.nlm.nih.gov/pubmed/21558267 - probably just read the abstract, bottom lines.

I'm happy too explain to anyone about caspases and how this system works - perhaps when we come to initial ideas and anyone is interested, I can draw a diagram and then just explain it further - Waqar.

1. 2 Placeholder

• Diagnostic tool for cancers
• material generating/ breaking down

* Ammonia generating bacteria

* Bacteria that break down certain polymers

* Hydrogen generation

* Bacteria that create biofuel

- lots of teams have tried this

* Bacteria that excrete sugars converted from CO₂

* An organism for cleaning potassium carbonate from fuel cells

* alkaline fuel cells?

* Toxic waste mediation

• Algae-based photovoltaic cells
• Sanitation use

* Marker for pollution status

• Nano wires

• Optogenetics

- already done a bit by Washington university's 2012 team

Idea #1

I proposed that we used optogenetics to control movement/behavior of vertebrate models such as Xenopus, however I think this approach would be particularly difficult and the consensus on this is that its a hard system to implement in practice. In particular, i feel that it doesn't have any far reaching impacts in terms of trying to then move forward (in respect to synthetic biology and contribution of parts etc) and has already extensively been tried and tested on say, mice. I think the start-up kits are around £2000 also. If anyone wants to expand on this and find out more, feel free to add anything below what I've written. - Waq.

In addition, after researching what the washington team did - i noted that their main problem was in the control of expression levels, which would be expected in such a system due to the fine level of control in respect to light that is required.

Reviews on this system, Karl Deisseroth is the pioneer of this system for behavioral manipulation by using light.

http://www.ncbi.nlm.nih.gov/pubmed/22430017

---

13/05/2014 Meeting:

Ideas:

Biological cellular automata

END7 diseases - find out one to tackle?

Photovoltaic algae

Bacteria with built in dormancy to produce protein spores

Degrading petroleum/oil in spills

Does dirty water contain some fuel that might produce light?

Biosensors

Detecting vitamin deficiencies and addressing them

Radioactive bacteria

Magnetic bacteria

Organic art (fractals/chaos)

---

24/05/14

Biological feasibility (Waqar)

Detecting vitamin deficiencies and addressing them

did literature searches and couldn't really find any system that people have used/engineered in which vitamins are detected by bacteria - potentially have to find out the mechanisms in which the human body detects and deals with vitamin deficiencies; (for iron - transferrin synthesis is controlled)

Found previous Igem competitions where people have engineered bacteria to produce certain vitamins, such as vitamin B9 by caltech http://openwetware.org/wiki/IGEM:Caltech/2008/Project/Vitamins 

others: https://2011.igem.org/Team:Johns_Hopkins

--

I came up with an idea in which we could potentially develop bacteria that can remove/uptake cholesterol - a particular type of bacteria called Lactobacillus (present in our gut as microbiota) is able too remove cholestorol -

Liong MT, Shah NP. Acid and bile tolerance and the cholesterol removal ability of Lactobacilli strains. J. Dairy. Sci. 88, 55–66 (2005).

other teams work:

https://2009.igem.org/Team:NTU-Singapore/Notebook - basically used E. coli and tried to create a system where you can visualize and degrade atherosclerosis plaques.

they also have a lot of cool ideas in their notebook that i've sifted through and decided too include the better ones here:

health & medicine

Create an insulin delivery system which response to low glucose level or time controlled release

Vitamin synthesis?

Hinder carcinogenics Maslinic acid (olive skin)-tritrepenoid compound Can we study anti-tumoral and apoptotic effect of this compound? E coli to interfere in the carcinogenic pathways Mimic the maslinic effect to the carcinogenic cells? Surface markers?

Bacteria to treat gangrene To eat up dead tissues

Collagen producing bacteria Using bacteria to breakdown blockage in blood vessels - how about producing bacteria that express an anatagonist of PDGF and VEGF - these are growth factors that promote angiogenesis, which is the growth of new blood vessels from existing ones > which happens a lot in cancer and is overactive (as cancers need a massive blood supply to become full scale tumors)

some teams have:

https://2013hs.igem.org/Team:Jefferson_VA_SciCOS - designed a system to promote angiogenesis under hypoxic (low oxygen) conditions

https://2011.igem.org/Team:Virginia - developed a system where angiogenesis is induced in wound sites (we could take their chassis/make up what they did to test the efficiency of our system)?

Cancer treatment - colon cancer(CA marker) Fusion protein to signal the expression of perforin (e coli as NKC) - a pretty cool idea, basically engineer killer bacteria that can recognize and kill cancer cells (particular markers characterize different types of cancer e.g prostate specific antigen for prostate cancers > could engineer a bacteria that detects PSA and then is activated/induced to kill prostate cancer cells?)

Bacteria to target the larvae

To separate Tamoxifen (possibly a chiral drug) by uptake the drugs into modified E Coli and bind it to the receptor inside the bacteria.

biosensor

Biosensor that sense the present of allergen and release drugs to prevent allergenic response

Mimic allergy response-to determine allergen?

Fingerprint detection

Can cells response to magnetic fields? Bird GPS ?? Magnetic field biosensor

Biosensor to detect cancer

environmental

E coli to detect toxins in food and flu strain in animals.

Biomask

For absorption

Create a water purifying system that recognize and trap toxic to uptake salt and others- sea water purification

Bacteria producing water for the use of photosynthesis so that plants can grow well in dry area Is it possible to construct water using certain metabolism pathway?

signalling

Multi-color display according to inputs to improve signal inputs DNA methylation as memory storage suffocate the cells baccine To construct guiding E Coli that guide pathogenic bacteria to a region of toxin/UV light.