Difference between revisions of "Team:IISER-Tirupati India/Description"

Module 1 :

DELIVERY AND COLONIZATION

This module deals with delivery and colonization of the genetically modified bacteria to the fallopian tubes.

Module 2 :

PROTEASE PRODUCTION AND HORMONE SENSING

The steps followed by the Genetically Modified Organism are progesterone sensing and cloaking the ovum from the sperm by zona hardening.

Module 3 :

KILL SWITCHES

This module deals with the kill switches the bacteria is engineered with to reverse the contraception and the biosafety.

We believe that our project is a useful application of synthetic biology as it’s tools and techniques allow us to use a chassis organism to produce a molecule that directly interacts with the gamete and not with the body and thus, comes with minimum side effects. Due to the tools and techniques of synthetic biology, we can also bring about one of the most important features of a contraceptive, which is reversal at will. This is achieved by engineering the bacteria with the inducible kill switch.

Through our project we wish to instigate a fresh perspective towards contraceptives and improve global reproductive health and rights by providing a safe and effective alternative.

Eco-friendly

Minimum side effects

Long term

Non-Hormonal

Ovum Specific

Reversible

The COVID-19 global pandemic has been affecting the world and India, being the second-most affected country, experienced several spans of complete lockdowns in two consecutive waves of infection. This limited our laboratory access and reduced the availability of resources to carry out this project. We have been rigorously working to provide the mathematical modelling for our project and hope to show the laboratory proof of concept with the experiments designed for the same. With a laboratory access of barely 2 months, we have worked on those experiments in an attempt to provide a proof of concept. While we were not able to carry the complete design, test and rebuild system on the laboratory front, it widened our understanding and engagement with stakeholders. We wish to instigate a fresh perspective towards contraception, and we believe that our project for iGEM 2021 has brought us a lot closer to achieve that and helped us break the dawn on a new era of modern contraception.

References : 

1. Bellizzi, S., Mannava, P., Nagai, M., & Sobel, H. L. (2020). Reasons for discontinuation of contraception among women with a current unintended pregnancy in 36 low and middle-income countries. Contraception, 101(1), 26-33.
2. Burkman, R., Schlesselman, J. J., & Zieman, M. (2004). Safety concerns and health benefits associated with oral contraception. American journal of obstetrics and gynecology, 190(4), S5-S22.
3. Beral, V., Bull, D., Doll, R., Peto, R., Reeves, G., van den Brandt, P. A., & Goldbohm, R. A. (2004). Collaborative group on hormonal factors in breast cancer: breast cancer and abortion: collaborative reanalysis of data from 53 epidemiological studies, including 83000 women with breast cancer from 16 countries. Lancet, 363(9414), 1007-1016.
4. Smith, J. S., Green, J., de Gonzalez, A. B., Appleby, P., Peto, J., Plummer, M., ... & Beral, V. (2003). Cervical cancer and use of hormonal contraceptives: a systematic review. The Lancet, 361(9364), 1159-1167.
5. Edlow, A. G., & Bartz, D. (2010). Hormonal contraceptive options for women with headache: a review of the evidence. Reviews In Obstetrics And Gynecology, 3(2), 55.
6. Hubacher, D., Chen, P. L., & Park, S. (2009). Side effects from the copper IUD: do they decrease over time?. Contraception, 79(5), 356-362.
7. Cooper, D. B., & Mahdy, H. (2021). Oral contraceptive pills. StatPearls [Internet].
8. Ramdhan, R. C., Simonds, E., Wilson, C., Loukas, M., Oskouian, R. J., & Tubbs, R. S. (2018). Complications of subcutaneous contraception: a review. Cureus, 10(1).
9. Shufelt, C. L., & Bairey Merz, C. N. (2009). Contraceptive hormone use and cardiovascular disease. Journal of the American College of Cardiology, 53(3), 221-231.
10. Lund University. (2016, March 4). Estrogen in birth control pills has a negative impact on fish. ScienceDaily.
11. Pelzer, E. S., Willner, D., Buttini, M., Hafner, L. M., Theodoropoulos, C., & Huygens, F. (2018). The fallopian tube microbiome: implications for reproductive health. Oncotarget, 9(30), 21541.
12. Pelzer, E. S., Willner, D., Huygens, F., Hafner, L. M., Lourie, R., & Buttini, M. (2018). Fallopian tube microbiota: evidence beyond DNA. Future microbiology, 13(12), 1355-1361.
13. Yu, B., Liu, C., Fredricks, D., & Swisher, E. (2020). Microbiome profiling of fallopian tubes. Gynecologic Oncology, 156(3), e26.
14. Grazon, C., Baer, R. C., Kuzmanović, U., Nguyen, T., Chen, M., Zamani, M., ... & Galagan, J. E. (2020). A progesterone biosensor derived from microbial screening. Nature communications, 11(1), 1-10
15. Burkart, A. D., Xiong, B., Baibakov, B., Jiménez-Movilla, M., & Dean, J. (2012). Ovastacin, a cortical granule protease, cleaves ZP2 in the zona pellucida to prevent polyspermyOvastacin cleaves ZP2 and prevents polyspermy. The Journal of cell biology, 197(1), 37-44.
16. Körschgen, H., Kuske, M., Karmilin, K., Yiallouros, I., Balbach, M., Floehr, J., ... & Stöcker, W. (2017). Intracellular activation of ovastacin mediates pre-fertilization hardening of the zona pellucida. MHR: Basic science of reproductive medicine, 23(9), 607-616.
17. Fahrenkamp, E., Algarra, B., & Jovine, L. (2020). Mammalian egg coat modifications and the block to polyspermy. Molecular reproduction and development, 87(3), 326-340.
18. Elbaz, M., & Ben-Yehuda, S. (2015). Following the fate of bacterial cells experiencing sudden chromosome loss. mBio, 6(3), e00092–e15. https://doi.org/10.1128/mBio.00092-15 (yqcG)
19. Holberger, L. E., Garza-Sánchez, F., Lamoureux, J., Low, D. A., & Hayes, C. S. (2012). A novel family of toxin/antitoxin proteins in Bacillus species. FEBS letters, 586(2), 132–136. https://doi.org/10.1016/j.febslet.2011.12.020 
20. Toxin-Antitoxin systems eliminate defective cells and preserve symmetry in Bacillus subtilis biofilms
    Zohar Bloom-Ackermann, Nitai Steinberg, Gili Rosenberg, Yaara Oppenheimer-Shaanan, Dan Pollack, Shir Ely, Nimrod Storzi, Asaf Levy, Ilana Kolodkin-Gal First published: 23 July 2016. https://doi.org/10.1111/1462-2920.13471 (yqcG and yqcF)
21. Brantl, S., & Müller, P. (2019). Toxin⁻Antitoxin Systems in Bacillus subtilis. Toxins, 11(5), 262. https://doi.org/10.3390/toxins11050262 (General info about toxin anti-toxins in bacillus subtilis)
22. Ni, L., Tonthat, N. K., Chinnam, N., & Schumacher, M. A. (2013). Structures of the Escherichia coli transcription activator and regulator of diauxie, XylR: an AraC DNA-binding family member with a LacI/GalR ligand-binding domain. Nucleic acids research, 41(3), 1998–2008. https://doi.org/10.1093/nar/gks1207 (xylR binding unbinding case: E coli)
23. Bhavsar, A. P., Zhao, X., & Brown, E. D. (2001). Development and characterization of a xylose-dependent system for expression of cloned genes in Bacillus subtilis: conditional complementation of a teichoic acid mutant. Applied and environmental microbiology, 67(1), 403–410. https://doi.org/10.1128/AEM.67.1.403-410.2001 (xylR)
24. Cameron, D. E., & Collins, J. J. (2014). Tunable protein degradation in bacteria. Nature Biotechnology, 32(12), 1276–1281. https://doi.org/10.1038/nbt.3053 (protein degradation by mf-Lon)
25. The Blue-Light Receptor YtvA Acts in the Environmental Stress Signaling Pathway of Bacillus subtilis
    Tatiana A. Gaidenko, Tae-Jong Kim, Andrea L. Weigel, Margaret S. Brody, Chester W. Price DOI: 10.1128/JB.00691-06 (Ytva to SigB activation)
26. Ching-Ying Chen, Shao-Chun Lu, Ta-Hsiu Liao
    Cloning, sequencing and expression of a cDNA encoding bovine pancreatic deoxyribonuclease I in Escherichia coli: purification and characterization of the recombinant enzyme, Gene, Volume 206, Issue 2,1998, Pages 181-184. https://doi.org/10.1016/S0378-1119(97)00582-9 (Bovine Dnase)
27. Noriko Suzuki, Naoki Takaya, Takayuki Hoshino, Akira Nakamura, Enhancement of a σB-dependent stress response in Bacillus subtilis by light via YtvA photoreceptor, The Journal of General and Applied Microbiology, 2007, Volume 53, Issue 2, Pages 81-88, Released June 14, 2007, Online ISSN 1349-8037, Print ISSN 0022-1260, https://doi.org/10.2323/jgam.53.81 
28. Haldenwang W. G. (1995). The sigma factors of Bacillus subtilis. Microbiological reviews, 59(1), 1–30. https://doi.org/10.1128/mr.59.1.1-30.1995 (SigB and gsiB)
    from Previous iGEM projects : Vagineering (2018) https://2018.igem.org/Team:Montpellier