Uday Ram is a third-yearundergraduate student majoring inPhysics at the Indian Institute ofScience, Bangalore. He is interestedin exploring the physics of exoticsystems, particularly looking at howcollective phenomenon leads to thestrange properties of these systems.When not doing physics, his entirefocus is on coding in python andplaying video games.

impact the time taken for in silicomethods for large networks, thusspeeding up research. Anotherpossible impact would be anincrease in the understanding ofroles played by different genesand proteins in various diseasestages and types and could furtherdrug/cure development. Suchinformation could potentially alsohelp in finding effective drugtargets to subdue various diseasesubtypes and support fasterrecovery.

One of the methods used during

How would you explain yourpaper’s key results to the non-scientific community?Every single living being isgoverned by their genetic make-up. This genetic material, DNA orRNA, is further divided into smallerunits called genes which encodeproteins and other machineryimportant for functioning. Thesegenes often interact amongstthemselves, in large networks.These networks result in all thedifferent cell types in an organism,ranging from neurons (brain cells)to nephrons (kidney cells), frommuscles to bones. Going on atangent, let’s talk about cancer.Cancer cells have been shown tobe of multiple types, such asmetastatic (the dreaded type thatroams around one’s body to findnew areas to latch on to), epithelial(the type that latches on andgrows) and hybrid types (stillunder research, but shown toexhibit greater drug resistanceand recurrent rates). We focusedon subtypes of Small Cell LungCancer (SCLC), a deadly cancerwith no known cure and abysmalsurvival rates. In silico methods(simulations done in amathematical framework) wereutilised, and results werecompared to the actual patientand experimental data to findanticipated similarities. We alsoperformed a successful reductionin the network size from 33 genesto essentially 4 partners,suggesting that such a largenetwork can be reduced to moreintuitive components that stillgives one the same subtypes insilico. This is indicative of an ideathat a large majority of genesresort to “groups”, whereindividual groups support/activate

VIGYANPATRIKA

Building in silico blocks of genenetworks involved in cancer

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First author: Lakshya Chauhan and Uday RamWork done in Dr. Mohit Kumar Jolly's lab, Centre forBioSystems Science and Engineering (BSSE), IndianInstitute of Science, Bangalore

Lakshya is a third-yearundergraduate student majoring inBiology at the Indian Institute ofScience, Bangalore. His interest liesin classical molecular biology anddevelopmental biology. Lately, he gotpiqued by interdisciplinary fields likesystems biology, biophysics, andbiomechanics. Besides work, he canbe found playing tennis andmultiplayer games.

amongst themselves but inhibitother groups. Hopefully, thisknowledge of such a reduction inlarge networks is universal innature and can be applied to othernetworks/diseases as well.Further, the two major groupsacted against each other, and sucha “tug of war” could potentially bepresent throughout biologicalnetworks!

Kishore is a third-year PhD student at the Center for Biosystems Science andEngineering, Indian Institute of Science, Bangalore. His interests are usingsystems biology to understand the diversity in biological systems. Specifically,he is trying to decipher the design principles of regulatory networks that allowcancer cells to bypass various barriers in the body. In his free time, he likes tosing and watch anime.

What are the possibleconsequences of these findingsfor your research area?If explored further, a universalpresence of “groups” could highly

UNDERGRADUATE SPECIAL

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Where do you seek scientificinspiration?Lakshya: YouTube at large is myperfect place for inspiration.Random videos and talks fromscientists and educators, and theamazing pace of research and thesheer magnitude of informationnot known to me is overwhelming,and a constant reminder to keeplearning. Documentaries, talks andresearch showcases help in this!

Uday: Science related articles.Whether in the form of socialmedia posts or news articles, thearticles on current research topicsis what inspires me to exploremore, read more about currentresearch and constantly thinkabout the problems that interestme. Also talking to researchersand attending their talks alsoinspires me a lot to learn aboutnew things in science.

grouping was the concept of an“Influence matrix”, which suggeststhat over the course of evolution,gene interactions grow to supportthe core “principle”, and the entirenetwork evolves around the same,enforcing the principle over aeons.The metric suggested by usprovides a quantifiable measure ofthe same and could beimplemented to find such coreprinciples in a multitude ofnetworks.

As undergraduate students,what motivated you to pursueresearch?Uday: Ever since my childhood, Ihave a desire to face the challengeof solving complex problems. Thefact that there are many unsolvedquestions to be solved made mepursue science. After coming toIISc, I came to know about theexistence of exotic systems both inPhysics and Biology. Thesesystems are often so complex anddiverse yet they follow the samelaws of physics. The desire tostudy them is what motivates meto pursue research.

Lakshya: This would be quite adifficult question to answer.However, if probed, I would say it’ssimply curiosity and amazementthat drives me. The very nature ofscience and how evolution drove,from very basic physics-basedprinciples to the rise of sentientcreatures and such complexbiological systems is somethingthat constantly overwhelms me. Iwould say it’s this boundlessnature of research that keeps myinterest piqued.

What was the exciting moment(eureka moment) during yourresearch?Uday: The most exciting moment Ihad while doing this project isfinding out the fact that this hugenetwork (SCLC network) can besuccessfully reduced to a 4 nodenetwork which preserves all theproperties of the bigger network.This implies that big and densebiological networks can in fact bereduced into smaller networksthat are both analytically andcomputationally easy to work with.

Lakshya: For me, it was when Iobserved that the concept of“Influence matrix” gives the sameresults as experimental andsimulation data. This might notseem huge, but it’s amazing tothink that just the network withoutany simulation and experimentaldata could give us a clear insightinto the properties arising fromlater. This was quite fascinating forme!!

Kishore: For me, it was when weidentified that such a largenetwork has only four states andwe figured out that this is due tothe nodes of the network forminggroups that act together. Thisimplies that the complexinteractions are not increasing thecomplexity of the system, but areworking together to preserve thesimplicity.

I will continue to work on thephysics of collective phenomenon.

Lakshya: Currently, I am stillexploring various fields of biology.While sure of my resolution topursue science, I am unsure aboutwhich field could be my niche. Ihope to stay in more quantitativefields of biology, and over mymaster’s figure my interests to thebest of my capabilities.

What do you hope to do next?Uday: At the moment I amexploring different fields ofPhysics to figure out which onesuits me the best. I am certain that

How do you intend to helpIndian science improve?Lakshya: I think the best way I canhelp Indian Science improve rightnow would be to keep honing myskill set and continue on mycurrently decided path. I do wishto take part in community

Lakshya: it is very important to notconstraint one’s thought processwhen it comes to interdisciplinarywork, and that’s my biggesttakeaway. Constantly reading upother fields, searching formultifaceted components to yourresearch has been an interesting,sometimes exhaustive butdefinitely fruitful process!

Kishore: Interdisciplinary researchthrives on putting various scienceand engineering disciplinestogether. It always helps if one hasthorough training in one of thedisciplines before entering thissetup, but communicating withexperts of various fields about theproblem one is working onbecomes a crucial part ofinterdisciplinary research. Not onlyis this a quick way to expand thehorizons of one’s thought process,but it also makes for a lot ofinteresting interactions.

What was your biggest lessonabout interdisciplinary researchsetup?Uday: My biggest lesson from thisinterdisciplinary project is that "tonever restrict your thinking to aspecific domain of Science whilesolving a problem". The questionsof "how" and "why" related to adomain-specific question oftenhas a very interdisciplinary answerto it. So as a researcher, it's alwaysgood to go through the work donein other disciplines which will helpin the long run.

outreach a bit more, where Iwould love to teach high schooland secondary students aboutresearch and science in a morefriendly manner than ourconventional schools. The waymost people are introduced toBiology and science at large is notoptimal, often driving studentsaway from even consideringresearch as a career option. Thisand the opinion that only “smart”people can do science are, in mypersonal opinion, the two biggestbane to Indian science. Doing mypart in changing these would bemy way of contributing.

Uday: Coming from a Physicsbackground, I feel that oftentimesstudents feel that physics is veryhard to grasp and is not worthgiving a shot. And also because ofthe huge popularity of JEE and IITsamong Senior High Schoolstudents, a lot of them really don'tget to see the active researchhappening in the field of Scienceand how amazing it is. Many

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The metric suggested by usprovides a quantifiable

measure of the same andcould be implemented to find

such core principles in amultitude of networks.

coaching institutes just focus ontraining the students to get marksin exams and won't makeattempts at demonstrating thebeauty of Science. So taking part incommunity outreach programmesand making an effort in bringingawareness about science amongparents and students willhopefully make some of thestudents interested in the field ofScience.

Kishore: In my opinion, the bestway to improve science in India isby giving undergraduate studentsa good environment to nurturetheir research aptitude. Theexcellent undergraduateprogramme at IISc is proof of that.Moving forward, I would like toenter academia and prepareteaching modules forundergraduates across thecountry to expose them to theexciting area of research andimprove awareness of variousopportunities available in the field.

Chauhan L, Ram U, Hari K, Jolly MK.Topological signatures in regulatorynetwork enable phenotypic heterogeneityin small cell lung cancer. Elife. 2021 Mar17;10:e64522. doi: 10.7554/eLife.64522.

Reference

Schematic

Lab website:https://mkjolly15.wixsite.com/cancersystemsbiology

Edited by: Pragya Gupta