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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 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

Tuberculosis, an infectious disease caused by Mycobacterium tuberculosis, affects nearly two billion people all over the world. India has the highest burden of TB with World Health Organisation (WHO) statistics for 2013 giving an estimated incidence of 2.1 million cases of active TB.

M. tuberculosis is a slow growing pathogenic bacterium with a doubling time of approximately 24 hours in tissues. This property of M. tuberculosis hinders rapid detection in sputum samples obtained from patients. The standard stain test does not work for these bacteria as they have a complex mycolic acid layer which prevents uptake of the dyes involved. Although a lot of effort has been focussed on treatment, diagnostics forms the basis of appropriate therapy for drug-sensitive and resistant strains.

Our aim is to leverage synthetic biology to develop a robust and self-sustained genetic device to help rapid diagnostics even in resource poor settings.

Multiple experiments targeting the different components of M. tuberculosis will be performed in an attempt to accelerate the growth of slow growing Mycobacteria. Mathematical modeling and computer simulations will be simultaneously used to model the various parts of the system.
Hence, with a joint approach of experimental testing and modeling, we hope to design a genetic device capable of combining the speed of PCR and the accuracy of microbial culture in the diagnosis of TB.

Therefore, our proposed solution will elegantly reduce the time span for TB diagnosis from days to hours in a cost-effective manner.

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 further population growth.We also attempt to base the 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 a possibly economic manner.