Rewriting the software of life

 -Akankshya Sahu

ଓଡ଼ିଆ ରେ ଏହି ଲେଖା କୁ ପଢ଼ିବା ପାଁଇ ଏଠାରେ କ୍ଲିକ୍ କରନ୍ତୁ ।

In your school days, you must have been taught about the scientists - Watson and Crick, who “decoded” life by discovering the double helix structure of DNA in 1953. The genetic parts (genes and the regulatory sequences) found in DNA are created from the codes that run the software of “Life”. All the information of life is encoded by using the four letters - A, T, G and C. Now, all it has to do is to form a sequence that forms a code for a protein, for example, insulin. If this sounds to you a lot like coding for software, then you’re right! If you have the codes of an organism, then you can basically recreate it for useful purposes. That’s what happens when biologists develop the mindset of engineers such as Craig Venter - to come up with the idea of rewriting the software of life

iGEM IISER Berhampur

The early 2000s proved to be a paradigm shift in the field of biology with the advent of “Synthetic Biology.” Since then it has drastically revolutionized science. It has the potential to design complex genetic circuits and operate them in living cells to impart new predictable functions. It has various research applications ranging from healthcare to biofuels. Some notable applications are releasing cancer drug molecules upon detecting tumor cells, protection of crops from disease-causing pathogens, engineering bacteria to decompose plastics and toxic chemicals in the atmosphere or water bodies in an eco-friendly way and whatnot. Interestingly, it is also the principle of the iGEM project of our team at the Indian Institute of Science Education and Research (IISER) Berhampur.

International Genetically Engineered Machines or iGEM competition, dates back its origin to 2004 at the Massachusetts Institute of Technology (MIT) when it started with just 5 teams. Till date, iGEM has grown into 352 teams of excited young students from universities all around the world. iGEM is a non-profit organization dedicated to inculcating research and education in the field of Synthetic Biology by creating an open community with opportunities for collaboration thus aiming to push the boundaries of synthetic biology. To participate in the iGEM Competition you need to register a team, which can contain a maximum 15 members, and should contain students from a wide range of departments, including biology , physics, computer science, math and chemistry.

The iGEM team begins meeting in January. With the help of the team’s advisors, students choose a project that matches their interests and take advantage of the resources and expertise of the hosting laboratory. Over the course of the semester, the team refines their project idea, designs new genetic parts, and begins to learn the lab skills they’ll need to accomplish their project.


And at last, all the iGEM teams present their project to the judges and peers at IGEM Giant Jamboree which are based on the concept of “design-build-test-learn” to create living systems and devices to solve local problems. And each team receives a medal based on satisfying the medal criteria and competing with teams all over the world.

Our team, iGEM IISER Berhampur for the first time participated in IGEM 2020 Competition last year and won Gold medal for their Project “FRAPPE”, we would be talking about their project some other day. This year is our second year at IGEM. 

                            

This year's team is a group of 15 students hailing from diverse disciplines of science, thus adding an interdisciplinary flavour to our iGEM Project - CODE M which stands for Cas Optimised DEvice for MDR-TB Detection. We are working to develop a rapid molecular diagnostic kit for Multidrug resistant Tuberculosis (MDR-TB). Antimicrobial Resistance is one of the greatest threats to the healthcare system and MDR-TB is one of them. India has the 2nd highest burden of MDR-TB in the world after China, with more than 1 lakh cases of drug resistant TB every year. As much as MDR-TB is a challenge, so is its diagnosis. Do you even know that, in 2018, around 56% of the estimated MDR patients were left undiagnosed?


The diagnostic methods currently used for MDR-TB are slow and expensive. Also in countries with inadequate health infrastructure, the diagnostic facility for MDR-TB is not available to all the patients. This leads to late or no diagnosis of MDR-TB, making it even more problematic. Though the Ministry of Health of the Government of India has various policies for eliminating this “silent pandemic,” these efforts are fruitless unless they reach the grassroot levels. So, our iGEM project focuses on resolving these issues. We aim to design a cost-effective, quick and reliable molecular diagnostic kit that can detect TB as well as MDR-TB from a sample for point-of-care testing. The main protagonists of our project are originally derived from bacterial immune systems used against viral infections i.e. the CRISPR/Cas systems - which gave rise to remarkable applications in biotechnology. These are the highly precise Cas14 protein and single guide RNA (sg RNA) which are synthesized using engineered E. coli bacteria.

Cas14 protein

They together form a complex and target the drug resistant mutations in the genes of the TB causing bacteria - Mycobacterium tuberculosis isolated from the sputum sample of a suspected drug resistant TB patient. Upon locating the mutations, it triggers a cleavage in the Fluorescence-Quencher (FQ) ssDNA reporters and the emitted fluorescence is detected with a mobile phone camera using fluorescence analyzing software.

This handy kit can be easily implemented in remote areas of India where financially challenged patients usually cannot afford doctor’s advice of proper diagnosis and potentially spread MDR-TB. As our kit will be fast, easy to handle and cost effective, patients will have access to the MDR detection in peripheral regions like rural areas. This will eliminate MDR-patients which used to go undiagnosed. The patients of TB and MDR-TB will also be separated in the early stages. Saving the precious time to cure MDR-TB patients which were earlier lost due to late detection and thus reduce the number of TB cases.

Lastly, after successfully working on the proof of concept of our project, we plan to design a working prototype of the kit. We are spreading awareness about this dreaded disease and educating the public about synthetic biology. We hope that our promising project will certainly help in combating Tuberculosis in India as well as the world.
You can follow our social media to stay connected with us and get more updates on our project: https://linktr.ee/iGEM_iiserbpr

References:

Title: Cryo-EM structure of the Cas12f1-sgRNA-target DNA complex

Reference: https://www.rcsb.org/structure/7C7L

(FYI: Cas12f1 is the same Cas14a1; just a different nomenclature)


Written By-
Akankshya Sahu

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