Dr. Ambuja Navalkar’s interview withBio Patrika hosting “Vigyaan Patrika,”a series of author interviews. Dr.Ambuja is currently working as anInstitute postdoctoral fellow at IITBombay. She has completed herdoctoral studies under the guidanceof Prof. Samir K. Maji in thedepartment of Biosciences andBioengineering, Indian Institute ofTechnology Bombay. Previously, shehas pursued her M.Sc degree inBiotechnology from the MaharajaSayajirao University of Vadodara,Baroda, and her B.Sc degree inBiotechnology from Ruia College,University of Mumbai. She isinterested in exploring the proteinaggregation linked with cancer andneurodegenerative disorders. Apartfrom research, she enjoys reading,good food, and solving puzzles. Shewants to pursue scientific researchfocused on fundamental processesin cells which can answer disease-relevant questions. Here, Ambujatalks about her work on prion-likep53 amyloid formation and its link tocellular transformation leading totumorigenesis published in theJournal of Cell Science.
in cells are reversed when wedisaggregate p53 using an in vitrosynthesized peptide inhibitoragainst p53 aggregates. Hence,our results provide evidence todirectly link p53 amyloid formationto cancer progression and providea model wherein the transfer ofp53 prions in an infectious manneracross cells can potentially spreadthe cancerous phenotype.
How would you explain yourpaper’s key results to the non-scientific community?Our body cells grow, proliferate,and die in a balanced manner.Several proteins inside the cellsregulate the proliferative pathwaysto maintain cellular homeostasis.If the cells experience stressconditions, many unwantedchanges, like DNA damage andmutations, can accumulate in thecell causing deregulation of celldivision, leading to diseases likecancer. Our research focuses onone of the possible causes ofcancer by studying the p53 tumorsuppressor protein, which is acellular brake against tumorformation. p53 has evolutionarilyconserved segments, which areaggregation-prone, that can driveits misfolding. p53 amyloidaggregates have been detected incancer biopsies linking it directly tocancer.
In their altered conformation(misfolded and aggregated), prionproteins act as infectious andtransmissible particles similar toviruses in human prion diseaseslike Creutzfeldt-Jakob Disease (CJD)and kuru. Our current study askswhether cancer can be a prion-likedisease caused by p53 amyloidinfection. We establish thatinduction of p53 amyloids in non-cancerous cells can enhance theoncogenic traits like resistance toapoptosis with high migrative andproliferative rates. p53 prions canbe transferred to the nextgeneration of cells, propagatingtransformative characteristics andincreasing cell survival. Cells withp53 amyloids in mice can establishtumors in mice models in vivo.Interestingly, the oncogenic traits
VIGYANPATRIKA
Prion-like p53 amyloids and their link tocancer pathogenesis
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First author: Ambuja Navalkar Work done in the lab of Prof. Samir K. Maji, at the Department ofBiosciences and Bioengineering, Indian Institute of TechnologyBombay (IIT Bombay)
What are the possibleconsequences of these findingsfor your research area?Our findings establish the possiblemechanism of cancer initiationand how the amyloid formationand spread of p53 aggregatescontribute to the cancerousproperties of the cells. The studyalso further highlights thepossibility that cancer can be aninfectious disease, althoughfurther in vivo studies are requiredto confirm this. Additionally, thedisaggregation of p53 amyloidsmay be implemented for targeting,if not all, but a subset of cancerswhere p53 aggregation isresponsible for canceroustransformation. Hence, this workpaves the path towards the studyof anti-aggregation therapeuticsfocusing on the p53 amyloidformation pathway to combatcancer uniquely.
What was the exciting moment(eureka moment) during yourresearch?During my research, there wereseveral exciting moments as wewere exploring the consequencesof p53 amyloid formation. Mymost memorable ‘eureka’ momentwas when I was performingmicroscopic imaging of the cells
induced with p53 aggregates, and Isaw that the p53 amyloids arecapable of transmitting throughcell generations. This observationwas pivotal to establish the prion-like transmissibility of p53 amyloidaggregates and led us to our in
What do you hope to do next?Currently, I am working as apostdoctoral researcher tounderstand the alterations incellular pathways due to p53amyloids, which lead to thetransformation of cells. I lookforward to exploring novelavenues to add to my expertiseand keep me motivated every day.In the long run, I am interested inpursuing research on theunexplored aspects of humandiseases like neurodegenerationand cancer for designing targetedtherapeutics.
How do you intend to helpIndian science improve?Since I am in a learning phase, Iseek to make the maximumcontribution through dedicatedresearch in biology as a scientist.In India, talent in young scientistsshould not suffer due to a lack ofexposure to challengingopportunities, research funding,and mentorship. Being a part ofthis scientific ecosystem, I hope toresolve these issues as aresearcher in my future journey. Ibelieve that science should not berestricted by geographicalboundaries and intend tocontribute to interdisciplinaryresearch beneficial to humankindglobally.
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this work paves the pathtowards the study of anti-aggregation therapeutics
focusing on the p53amyloid formation pathwayto combat cancer uniquely.
Navalkar A, Pandey S, Singh N, PatelK, Datta D, Mohanty B, Jadhav S,Chaudhari P, Maji SK. Direct evidenceof cellular transformation by prion-like p53 amyloid infection. Journal ofCell Science, 2021;134 (11): jcs258316.DOI: 10.1242/jcs.258316.
Reference
Edited by: Vikramsingh Gujar
Where do you seek scientificinspiration?To quote Richard Feynman, “Studyhard what interests you the mostin the most undisciplined,irreverent and original mannerpossible.”
I believe that my scientificinspiration essentially comes fromthe desire to seek answers tobiology’s unsolved puzzles. Mypassion for science is the alarmclock which wakes me up everymorning, and I enjoy the thrill ofdesigning new experiments. Apartfrom this, my mentor and labmates have always beenenthusiastic about scientificdiscussions, which have got methrough the crests and troughs ofacademia.
Prof. SK Maji lab:https://www.bio.iitb.ac.in/~maji/
FIGURE 1: p53 amyloid formation and its implicationsin cancer pathogenesis.
vivo studies. We are currentlyexploring the effects of this prion-like transmission on cellularpathways.
