What I cannot create, I do not Understand

Imagine a world where children play with Lego blocks to build castles and cars. This is our world today. Now take a leap 50 years into the future.

Lego blocks might just fade away into units of life, or genes, being assembled into newfangled forms of living, breathing entities. Rewiring cellular architecture could become child’s play for scientific investigators in order to make the world a tenable version of the paradise it once was. Yes, it may sound wild and absurd, but such is indeed the potential of the discipline we call synthetic biology. 

Over the past few decades, the field of synthetic biology amassed considerable attention from researchers in almost all disciplines. With a spirited community of scientists, synthetic biology aims to use common techniques from engineering and biology to control cell behaviour. This field aims to revolutionise human lives by using biological principles to drive manufacturing. 

Engineering microorganisms is not something unknown to us. Using bacteria for fermentation or as factories to mass produce enzymes and drugs have been in the picture for a long time. What makes synthetic biology, or “Synbio” different, is the view of life as a machine. A machine, composed of modules, or units. These can be “programmed”, rearranged or tuned to realise remarkable feats. And, the quote in the title by physicist Richard Feynman, aptly describes the goal of Synbio – to understand the nuances of life by fundamentally creating it. 

Lying at the intersection of several branches of science, Synbio holds immense potential in enabling researchers to understand the basics of natural systems, as well as in applying these to generate new biological circuits. These uses run the gamut from health and environmental to energy applications. Synbio can make triumphs such as therapeutic programmable cells, eco-friendly plastics and fuels and artificial meat, living realities. 

As the pace of Synbio has increased, scientists have made efforts to assemble people from varied mindsets to allow rapid exchange of ideas during international conferences. iGEM, or International Genetically Engineered Machine was conceived as a venture to nurture education and collaboration in this field, in the early 2000s. A leading competition for undergraduates in synthetic biology is hosted by this organization every year. Students come together from all over the globe to participate and compete. Multidisciplinary work is encouraged to expand the Synbio toolkit by building solutions to daily problems via unique ideas. We use core concepts of “design-build-test-learn” to craft systems and devices using a repository of biological parts and mathematical approaches. These projects also focus on using various integrated outreach endeavours to leave a far-reaching impact on human lives.

Here, I would like to share the ideas of our iGEM team from the Indian Institute of Science Education and Research (IISER), Berhampur for this year (FRaPPe – FRET Based ranker for Proteins and Peptides). It revolves around the Dengue disease. A mosquito borne viral disease, Dengue has plagued numerous countries over the past years. With nearly 390 million cases reported annually, the virus has reached more than 120 countries. In India, several states which had no reported cases before, are now observing a widespread incidence of Dengue. But, in the wake of COVID-19, does this really warrant our attention?

Normally, Dengue fever is not very dangerous. The patient suffers from fever or rashes and recovers in a few days. In some cases however, this can progress to severe stages, such as Dengue Haemorrhagic Fever and Dengue Shock Syndrome, claiming lives. To further complicate affairs, Dengue virus exists in four different serotypes, or variants, making it quite tasking to develop a universal remedy. There are still no effective antiviral drugs or vaccines for this disease. With possibilities of widespread epidemics looming just around the turn of the COVID-19 outbreak, and a sparsity of viable treatment options, this virus might potentially become the next challenge to jeopardize mankind. 

Our  team aims to ameliorate the situation by developing new tools to study the virus and design drugs against it. This system will focus on the interactions taking place between different proteins produced by the virus, and their host targets. The Dengue virus uses many of these interactions to affect our immune responses. It then divides and spreads throughout our tissues. Because of the complicated pathways involved, there are several knowledge gaps in our understanding of the disease. By engineering human cells to express these proteins, their interactions will be regulated and measured using fluorescence based approaches. This will allow investigation of the proteins of interest by simply attaching other molecules to it that can be studied through physical or chemical means- in essence, a “reporter” system. 

The target interaction between a dengue virus protein and host protein to be blocked. These proteins form a complex which obstructs a crucial antiviral defence pathway in the host.

A drug that targets and breaks the interaction of two of the proteins in the Dengue virus pathogenesis pathway can thus, hold promise as a possible intervention game plan. Building the “reporter” system by assembling modules to study this process and testing its efficiency using the drug is the essential focus of the project. Hopefully, if the endeavour succeeds, it can serve as a convenient instrument for scientists to speed up therapeutic design for years to come.


To read more about our project (Team iGEM IISER Berhampur), visit our website:

https://sites.google.com/iiserbpr.ac.in/igemiiserberhampur/home

To join or support us in various outreach endeavours visit the links below:

https://linktr.ee/iGEM_iiserbpr

To know more about the iGEM competition visit the link below:

https://igem.org/Main_Page

The team members, Project FRaPPe 

References:

  1. Cameron, D. E., Bashor, C. J., & Collins, J. J. (2014). A brief history of synthetic biology. Nature Reviews Microbiology12(5), 381-390.
  2. Glass, J., Collins, J. J., & Romesburg, F. (2018). The future is synthetic biology. Cell175, 31391-6.

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