Team:ColumbiaNYC/Brainstorm
Brainstorming
Here are some other ideas we came up with this summer that future iGEM teams can incorporate into their own projects:
Nav1.7 is a voltage-gated sodium channel expressed on nociceptive neurons, neurons responsible for transmitting pain signals
from the PNS to the CNS. Nav1.7 is essential for normal pain sensation; if it is not expressed, the patient will
not feel pain at all, and if it is overexpressed, the patient will experience chronic pain (20% of the population
worldwide). Nav1.7 is therefore a prime therapeutic target whose blockage by an T-cell antibody would mitigate
pain, with the T cell acting as a potential analgesic. A circuit would be designed so that once the T cell binds
to the epitope, a chimeric antigen receptor (CAR) could be engineered to be drug-switchable so that the T cells
are controllable. This way, a physician could titrate cell activity and control timing with a drug, which is
potentially safer. An accessible drug that suppresses pain would not only be of much relevance to medicine, but
also in our daily lives.
Cancer is the second greatest cause of death in the United States. Nevertheless, many biomarkers have been found for various
types of cancer, such as pancreatic, breast and prostate cancer. These biomarkers that are intrinsic to a particular
form of cancer can be applied to cancer diagnostics and detection, given a specific receptor and reporter. G
protein coupled receptors, along with yeast, can be used as a reliable method of cancer detection when enhanced
with directed evolution (to induce sensitivity to high concentrations of biomarker, but not low concentrations)
and expressed alongside GFP in the presence of a strong signal.
Hemophilia A, the most common type of hemophilia, is caused by a missing or defective factor VIII clotting protein. Current
treatments are time-consuming, expensive, and unpleasant. Our idea is to create a probiotic that secretes coagulation
factor VIII into the small intestine to be absorbed into the bloodstream. We would obtain cells with mutations
in the thioredoxin reductase gene (trxB) and glutathione reductase gene (gor) in order to make E.coli’s intracellular
environment oxidizing. This is necessary for the oxidation of the disulfide bonds in the Factor VIII proteins,
which along with the expression of a heterologous protein disulfide isomerase and a heterologous chaperone protein,
enhances the yield and solubility of Factor VIII proteins. The proteins will be expressed in
E.coli, given the appropriate auxotrophic control sequences and gene casette. The production of the factor
VIII proteins will be tested via Western Blot, and the activity of the proteins will be observed with a APTT-based
one-stage assay. Finally, the solubility of the proteins was evaluated by verifying the presence of the proteins
in an aqueous fraction (after centrifugation).
Most collagen products used for biomaterials or biomedical devices are extracted from animal sources. However, application
of animal collagen carries the risk of pathogen or prion contamination and the possibility of causing allergies.
Other problems include the lack of standardization for animal collagen extraction processes and the inability
to modify collagen sequences to achieve different biological purposes. Compared with collagens extracted from
animal tissues, recombinant collagens are highly pure, disease free, consistent among batches, and amendable
to sequence modifications and large scale production. Such recombinant collagen can be made by
E.colibacteria, allowing for the use of versatile and cheap collagen, especially in the fields of regenerative
medicine and tissue engineering.
Here are some more ideas expanded upon in depth:
