Our Partnership with Guangxi-U

Over the course of the semester, our team has been collaborating with the Guangxi-U iGEM team from China. After seeing our website in August, Dr. Hongying Zhong reached out to our PI, Dr. Brian DeDedecker, about working together. Over time, we built a rapport and agreed to help each other in our research. While Dr. Zhong is an expert in mass spectroscopy, our lab has had much more practice with wet lab work, specifically with the use of Golden Gate enzymes and reactions.

Last week, Dr. DeDecker met with Dr. Zhong again, and helped the Guangxi-U team by teaching them more about Golden Gate reactions—our lab’s speciality. We were also able to answer their questions about cell culture techniques. Their team is currently working on engineering E. coli that can live on lactate as a chassis for triple negative breast cancer (TNBC) therapeutics. Since we are both working on cancer therapeutics through our genetic engineering projects, we saw that this could be a beneficial collaboration to us both. Their team found that taxol, like their lactic-acid eating bacteria which boosts the response of macrophages in the anti-tumor immune response, also boosts macrophage transformation in the same way. In both responses, M2-polarized macrophages are transformed to the M1-like phenotype in a TLR4 dependent way. Their team will benefit from having both the engineered bacteria that lives off of lactate and bacteria that expresses a taxadiene synthase construct. Meanwhile, the Guangxi-U iGEM team is also developing a mass spectroscopy technique that would allow us to identify where in the MVA pathway the 5’ carbon on taxadiene gets hydroxylated, as well as give insight to how and where T1 production occurs in E. coli. We could use the data from Guangxi-U’s mass spectroscopy to further refine our constructs and get closer to our engineering goal of producing baccatin III. With this information, we will be able to identify which constructs are the most promising for further research.

References

1. Schmid, P. et al. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N.ew Engl. J. Med. 2018, 379, 2108–2121.
2. Naik, A.; Decock, J. Lactate metabolism and immune modulation in breast cancer: a focused review on triple negative breast tumors. Fron. Oncol. 2020, 10, 598626.
3. Tariq, M.; Zhang, J.; Liang, G.; Ding, L.; He, Q.; Yang, B. Macrophage polarization: anti-cancer strategies to target tumor-associated macrophage in breast cancer. J. Cell Biochem. 2017, 118, 2484-2501.
4. Zhong, H. et al. Mass spectrometric analysis of mono- and multi- phosphopeptides by selective binding with NiZnFe2O4 magnetic nanoparticles. Nat. Commun. 4:1656 doi: 10.1038/ncomms2662 (2013).