Away from home: CRISPR and I

Posted on 31 Jan 2017 by Subhra Priyadarshini

After a gap, our ‘Away from home‘ blog series is buzzing again. Here we feature promising young Indian postdocs working in foreign labs. The postdocs featured in the series recount their experience of working in foreign lands, the triumphs and challenges, the cultural differences and what they miss about India. They also offer useful tips for other Indian postdocs headed abroad. You can join their online conversation using the #postdochat hashtag.

Our ‘Away from home’ interactive map now features 43 bright Indian postdocs from around the world. Please feel free to suggest names of postdocs from countries and disciplines we haven’t covered yet.

Today, we hear from Samrat Roy Choudhury, a postdoctoral fellow at the Myeloma Institute, University of Arkansas for Medical Sciences (UAMS), USA. Samrat, an alumnus of Indian Statistical Institute (ISI), Kolkata, tells us about his pathbreaking work in CRISPR-based gene editing, its implications in cancer therapeutics, his first snow experience in the US and his tough journey to reach there.

Samrat Roy Choudhury in front of the Bindley Bioscience Center, Purdue University, USA.

Always loved science

Science, particularly biology and chemistry, were my favourite subjects in middle and high school. I aspired to become a high-school teacher or a college lecturer. When most of my classmates opted for engineering or medicine as careers, I chose the longer path.

Late Prof. Swapan Das at Kolkata’s Asutosh College was my inspiration in biological sciences. After a Zoology masters from University of Calcutta, I got a chance to work at the lab-bench of the National Institute of Cholera and Enteric Diseases (NICED), Kolkata. The experience was fascinating and convinced me to pursue research as a career – I enjoyed designing experiments, executing them and using analytical skills to interpret data. It’s empowering to think that my research might make a small but powerful impact in the way we combat diseases.

During my PhD in nanobiotechnology at the Biological Sciences Division of the Indian Statistical Institute (ISI), Kolkata, I got the chance to design and develop several nanoparticles and nano-conjugates of antimicrobial implications. I was amazed to see how the same chemical elements behaved dramatically differently at nano-level compared to their micronized state. I was fortunate to meet and work with several eminent physicists and biologists, such as Prof. Dipankar Chakravorty (IACS) and Prof. Ratanlal Brahmachary (ISI) who re-kindled the passion for research and innovation in me. They taught me that science is not simply an act to be performed in a confines of a laboratory but the inner vision to explore our surroundings.

I wanted to continue exploring novel biophysical and biochemical tools, beyond the area of nanoparticle research. I was particularly interested in evaluating the potential of bioengineering tools in deciphering intriguing bio-molecular complexities. The prime search criteria for my postdoctoral training was, therefore, aimed at finding a group, which is dedicated in developing innovative and functional biomolecular tools. I chose to work with Prof. Joseph Irudayaraj at the department of Biological Engineering at Purdue University, USA.

CRISPR and cancer therapeutics

I spent three years (2013-2016) at Purdue as a postdoctoral research assistant, where I was exposed to a new arena of bio-engineering applications. During this period, I focused mainly on designing and targeting novel synthetic protein tools such as TAL (transcription activator like elements), or CRISPR-Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats) to the cancer epigenome for site specific modifications with a purpose of therapeutic interventions.

Cancer, as the title of Siddhartha Mukherjee’s Pulitzer-winning book says, is indeed ‘The Emperor of All Maladies’. My team’s research efforts at Purdue resulted in CRISPR-based epigenomic editing at the promoter of a known tumor suppressor gene BRCA1. We utilized a deactivated version of the Cas9 (dCas9) enzyme, fused to a demethylating enzyme TET1, which specifically demethylated the BRCA1 promoter. By achieving these loci specific demethylation, we succeeded in increasing BRCA1 expression and obtaining a significant reduction in cancer cell proliferation. This illustrated the novelty of using CRISPR based bioengineering tools to promote targeted epigenetic corrections and broadening the scope of next generation cancer therapeutics.

Subsequently, I joined the Myeloma Institute at the University of Arkansas for Medical Sciences (UAMS). In addition to studying the targeted epigenetic regulations in high-risk multiple myeloma (HRMM), I’m also engaged in identifying the aberrant epigenetic signatures of HRMM.

Of the first snow fall

I belong to Kolkata, a city which nicely orchestrates the core cross-over values. Hence, the transition to USA was smooth for me with a few minor awkward incidents. In any case, a postdoc’s life mostly revolves around laboratories, so the scope of social events remained limited for me. I witnessed the first snowfall in my life in USA, which was wonderful. I remember, my wife and I made a miniature snow-man (she called it a snow-baby), which grew bigger and bigger with subsequent snowfall. I however, do not enjoy hopping like penguins over 6 inches of snow all through winter.

USA has historically served as a key destination for scholars. In larger cities and universities, life can be busy but also very entertaining. For instance, Purdue’s campus was very cross-cultural with a diverse array of restaurants, multilingual people and a reputation for academic excellence. Both at Purdue and UAMS, I met very talented, hard-working, professional and helpful people. Lab-meetings, seminars, and inter-research group discussions are common, meant to bring out the best in people. USA could also be a wonderful destination for travel and recreation. The country is picturesque, has everything from acres of green meadows, amazing fall colours and an array of skyscrapers and ultra-modern works of architecture.

Postdoctoral life in USA is extremely challenging. At times it can be frustrating and even depressing. I realized, like thousands of other postdocs, the meaning of the maxim ‘publish or perish’. Continuous pressure at work, in addition to thousands of miles of distance from parents and friends, can be excruciating at times.

Tips for postdocs

Please do not give up on your dreams. I grew up in a lower-middle class family with continuous pressure of stable employment. I used to take private tuitions beyond the lab hours and was so exhausted sometimes that I slept off in public transport missing the right stop. But I never thought of leaving research or academics. When your innovation and hard work pay off, the absolute joy of that moment alleviates all injury and bitterness.

India, first choice

I miss my parents and friends. My parents are old and have limited access to video-chatting. A part of the ‘worried’ me, hence always remains with them.

I’m very keen on starting my own laboratory in India. My primary research focus would be the study of physicochemical influences of nutrients, nanoparticles and chemical compounds/drugs with respect to their instigation of epigenetic modifications. Furthermore, I would be interested to correlate their influence in various disease models. With a suitable offer, India would be my first choice.

Scientific writing: A very short cheat sheet

Posted on 17 Jan 2017 by Subhra Priyadarshini

Indigenus brings you some interesting and relevant posts from sister blog Naturejobs, a leading online resource for scientists in academia and industry who seek guidance in developing their careers. The blog delivers a mix of expert advice and personal stories to help readers review, set and achieve their career goals.

Today, researcher-turned-science-writer Meenakshi Prabhune talks about the golden rule for effective science writing — keep it simple.

The life of a researcher is incomplete without undergoing the trauma of writing scientific documents: papers, grants, protocols, theses, and so on and on. Most researchers find this stressful, time-consuming, and difficult; and, despite the enormous time and effort invested in writing, I for one often come across close-to-incomprehensible papers while digging through the literature. Why is that the case, and how do we fix it?

In my opinion, clarity breeds precision, and vice versa. It’s impossible to summarise a finding precisely if you haven’t understood it. A vague sentence that rambles on into the woods without a solid point will only confuse your readers, and indicate a lack of understanding on your part. Research your references and data thoroughly to avoid this. Preparation is an essential ingredient when writing clear and precise sentences.

Let’s consider the actual writing process—you write a sentence, realize you need a reference, search around for it, re-read the sentence, decide it’s not perfect, edit it, and wonder if you’ll ever finish at this speed.

Sounds familiar? Here’s something I wish I’d known sooner: writing and editing are separate processes. It’s perfectly fine to envision the end product and work in that direction, but don’t expect the first draft to be flawless. An effective writing method is to actively think about the content, write an entire paragraph or two—or three, or four—and then edit for perfection. This approach ensures a logical flow of sentences, as you’re following your own train of thought at a decent pace.

Meenakshi Prabhune

In terms of style, a healthy mix of short and long sentences is the key to a good manuscript. Short sentences read well. Long sentences with multiple conjunctions, punctuations, parts, pieces, bits, bobs, tenses, disclaimers, derivatives and definitions, although grammatically sound, are exhausting, and they also require extra attention on the reader’s part—that is, if the reader hasn’t given up already. Point proven?

Lastly, I think an important issue is that researchers—especially young researchers—often focus far too much on ‘sounding smart’. Your boss, peers, and the rest of the world are going to read something written by you for the first time, and there is often a real fear of coming across as stupid. Researchers should remember that the science in their paper is the only thing they need to validate their intellect.

Your aim while writing should be to spread your scientific findings to a large audience. So, confusing your readers—or potential reviewers—with complicated sentences and thesaurus entries will only discourage them from reading further. Write to express, not impress.

[Meenakshi lives and works in the Bay area, California. You can read her blog, that covers science and travel, here.]

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