Team:IISER Pune

Indian Institute of Science Education and Research (IISER), Pune, India

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Welcome to the team page of the Indian Institute of Science Education and Research, Pune's iGEM 2015 site

• Since 6-May-2015 we now have a team of 10 (nice round number) UG members, 2 advisors and one PI!
• We are currently meeting on every alternate day to chalk out our workplan.
• Context of the problem: TB kills more people than most other diseases in the developing world. Diagnostics is either by Zalh-Nielsen staining (1884). Recent advances in PCR have led to DNA based diagnostics. But cost can be a barrier.

Project Description

Our project aims at finding a relatively rapid and cost-effective method for diagnosis of tuberculosis through the approach of synthetic biology. We plan to construct a robust and self-sustained genetic device comprising of three functional components- first one to detect the sputum samples positive with TB, second one to hijack/overclock the Mycobacterium tuberculosis cell cycle and thereby accelerate the bacterial cell division, and the third one to terminate the cellular growth on attaining a stipulated density hence preventing the pathogen outbreak. We strategise to package our genetic device in phi-square gfp10 phage, which is selectively infectious to Mycobacterium. Our strategy is expected to mechanise in the following manner- On entering the bacterium, the phage takes over the genetic machinery of the cell. It then causes the cell to constitutively produce a coloured pigment/protein. This acts as a response to verify the presence of M.tb. The genetic oscillator (Smolen/Variable-link) increases the frequency of oscillations of dnaA & ftsZ (cellular components responsible for replication initiation & septum formation respectively). This results in quickening of chromosomal replication & cell division and hence giving us a significant cellular population in a small time frame. Once a particular cell density is achieved in a given sample, the AHL based quorum sensing circuit causes the expression of toxin gene- ccdB, restricting the further population growth.We also attempt to base he behaviour of our genetic components and guide our experiments through few mathematical models as well as computer simulations. Therefore, our solution elegantly reduces the time span for TB diagnosis form days to hours in an possibly economic manner.