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, which is not currently the case. This way, a physician could titrate cell activity and control timing with a drug, which is potentially safer.

There are products (such as polymer based gels) that rapidly stops blood loss However, they require physical application to the wound, meaning that they would not be able to stop internal bleeding and would not be practical to chronic or potentially-widespread bleeding such as hemophilia. Our cells would receive either a physical or chemical signal in response to a blood vessel being broken changing the extracellular pressure or releasing tissue factors through the extrinsic coagulation pathway, respectively. This would either induce a promoter, resulting in either a positive transcription loop or activation of an allosteric modulatory switch. The circuit would output cofactor 10a (FXa), the catalyst for the coagulation pathway. The system would be tested in cell culture and murine models. Tissue Factor is released by the ruptured walls 1 Factor 10a (Xa) molecule can catalyze the formation of 1000 thrombin molecules

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).