Immunotherapy: the next frontier in rational anti-cancer drugs?

March30

The recent approvals of chimeric antigen receptor t-cell (CART) therapy for commercial use has triggered renewed interest in both the immune-biology and molecular details of how cancers evade the immune system, but also generally the utility of “Synthetic Cell Biology” in “live therapeutics”.  I like to distinguish “live therapeutics” from those that aren’t alive in terms of the complexity. And given the idea of a cell as the smallest unit of life, this is all the more interesting. The “poison”, “burn” and “kill” strategy of the magic bullet (Paul Ehrlich) has a long and effective history. However, for cancer which is a multifactorial non-communicable disease, this paradigm has perhaps been superseded by an approach based on our understanding of the biology, and our ability to manipulate endogeneous functions. While ImmunoTherapeutics (1) are already showing promising results, my own interest is piqued by our ability to convert a molecular understanding of immune cell molecular biology to modify our own cells (2).

REFEFERENCES:
1) https://www.cancer.gov/publications/dictionaries/cancer-terms/def/immune-checkpoint-inhibitor
2) https://www.cancer.gov/about-cancer/treatment/research/car-t-cells#living-drug

Synthetic morphogenesis at EMBL Heidelberg

March30

The use of synthetic biology in engineering biological systems has been rapidly expanding. the conference at EMBL Heidelberg from 17-20 March 2019 on “Synthetic Morphogenesis: From Gene Circuits to Tissue Architecture” highlighted this in the context of understanding growth and developmental morphogenesis. It brought together an unusual combination of researchers ranging from:

  • in vitro reconstitution of cytoskeletal networks
  • giant unilammelar vesicles (GUVs) for encapsulating proteins: towards synthetic cells
  • rebuilding gradients of morphogens by engineering cells
  • organoid models of tissue morphogenesis
  • engineering blastulas and developing embryos predictively modify developmental outcomes

Post-publication review and PLOS’ experiment with the Synthetic Biology Collection

October28

An inducible luxI system (iptg) to produce the AHL above a threshold Pt. Kadam et al. (2016)

The iGEM 2015 synthetic biology contest was an important one for us. It marked our first attempt at putting together a project from IISER Pune. But beyond the novelty for us, many things were different this time around (#igem2015). First off, no preliminary or elimination rounds.

Secondly, we (yes, some self-backpatting here) organized an India Meetup in the run-up to the Jamboree. And third, and interestingly, the journal PLOS One (Public Library of Science) decided to use this as an opportunity to launch the PLOS iGEM collection, as a sort of meta-list, connected to iGEM. They decided to also go the radical way- with post-publication review. Time will tell how this latter experiment works out. And naturally our team’s efforts are there. With a lot of hard work put in by Snehal Kadam well after the contest and some griding-the-article together by mining long-forgotten (1 year ago!) protocol books, and some frantic emailing and interviewing, we managed to pull it off. You can read it here “Mycobacterium Revelio: Characterizing and Modeling Genetic Circuit Components towards a Bacterial Detection Tool”. The first 10 authors are BS-MS undergraduate students. Manasi and Neha are PhD students.

iGEM

July26

In 2015 we hosted an iGEM team form IISER Pune. The theme was Mycobacterium revelio- in the spirit of Harry and his revleaing charm. Mycobacterium tuberculosis is prevalent worldwide, but India tops the charts for prevalance. Our project aimed to produce a novel diagnistic tool for low cost and rapid detection.

L to R: Snehal, Ira, Prachiti, Prashant, Yash and Siddhesh.

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