Research Projects

Project Summary Scientific Rationale: GLP-1 is a peptide hormone that is a promising therapeutic candidate for treating obesity and diabetes. However, it has a short serum half-life (∼2 min) since it is easily degraded by serum enzymes, limiting its therapeutic use. Glycosylation and N-glycan modifications of GLP-1 increases its serum half-life and in vivo activity. GLP-1 analogs can help patients lose up to 8-20% of their body weight. While the beneficial effects GLP-1 analogs are impressive, they have also shown harmful side-effects. Is it possible to achieve a similar beneficial effect by raising the levels of natural GLP-1 and GIP through diet – without resorting to weight loss drugs? The research focus is on how patients can get a similar beneficial effect by raising the levels of natural GLP-1 and GIP in diet – acting like a natural form of Ozempic - without using the weight loss drugs. By using Synthetic Biology (SB) and Genome Editing (GE), it might be feasible to engineer edible algae fortified with natural GLP-1 and GIP polypeptide hormones to use as nutraceuticals for slow and continuous in vivo delivery, to treat obesity and T2D. Novelty: Rapid advances in SB and GE make it feasible to engineer edible algae fortified with natural GLP-1/GIP polypeptides, to use it as a slow in vivo delivery platform. As nutraceuticals, engineered edible algae will be a novel and safe way to treat obesity and T2D. This project is an excellent example of how to use Bioinformatics, SB and GE for Collaborative Research in Biological and Biomedical Sciences. If successful, a similar approach, could be used for the delivery of edible vaccines and other drugs to treat various human diseases. The proposed program will uplift the research innovation stature of the departments and host institute. Objectives: 1) Design and assembly of codon optimized GLP-1/GIP polypeptide transcription units for high expression in edible algae; 2) Targeted insertion of GLP-1/GIP transcription units into edible algae and monitor GLP-1 and GIP polypeptide expression levels. 3) Animal testing using obese mice model for weight loss. 4) Establish for large-scale industrial production of edible algae fortified with natural GLP-1/GIP polypeptides using bioreactors. 5) As a sub project, design and construct a compact functional CRISPR/Cas using machine learning and AI. Use SB for de novo synthesis of the compact Cas9 and test it in GE applications. Methods: GLP-1/GIP transcription units will be assembled using SB. CRISPR/Cas9 editing will be used to engineer the edible algae. Genomics and proteomics will be used to quantify GLP-1/GIP expression levels. Functional validation will be done using algal extract to induce insulin production in pancreatic beta cells and measuring intact insulin by Quest Diagnostics assay. Expected outcome: Edible algae fortified with natural GLP-1/GIP peptide hormones. Design and de novo synthesis of a compact Cas9 for use in various gene therapy applications.