Bhabatarak Bhattacharyya (1944–2021)
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PERSONAL NEWS Bhabatarak Bhattacharyya (1944–2021) Professor Bhabatarak Bhattacharyya, the development of science and research (B-ring), which anchors the A- and fondly known by his nickname ‘Bablu’, in India. He established his lab at the C-rings. His structure–activity studies passed away on 6 May 2021. He was a Biochemistry Department of Bose Insti- indicated that the A- and C-rings of col- distinguished biophysicist and made stel- tute, Kolkata, India. His lab was the first chicine comprise the minimum structural lar contributions in understanding the tubulin laboratory in the country and he features of the molecule necessary for its biophysical and pharmacological proper- was lovingly known as the microtubule- high-affinity binding to tubulin. The role ties of tubulin, the eukaryotic cell organizing centre of India. Several of his of C-7 substituents on the B-ring was not division protein. Originally a chemist, graduate students are now leading micro- known. His group determined the thermo- Bhattacharyya set out to build his career tubule laboratories in India. Microtu- dynamic parameters for the binding reac- on applying biochemical and biophysical bules formed by the polymerization of tions of four B-ring analogs of colchicine techniques to address the fascinating the tubulin dimer of alpha and beta sub- with tubulin: deacetamidocolchicine mysteries of biology, specifically the units, provide the structural framework (DAAC), 1 deacetylcolchicine (NH2- eukaryotic cytoskeleton. For more than to the cells to carry out important DAAC), demecolcine (NHMeDAAC) four decades, he led the investigation of processes such as cell division, cell and N-methyldemecolcine (NMe2-DAAC) several aspects of the cytoskeletal pro- polarity and cell motility. He showed that using steady-state fluorescence spectro- tein tubulin primarily on tubulin–drug the C-terminal tails of tubulin, previously scopy. The study indicated that the interactions, folding and unfolding path- presence of B-ring per se did not affect ways of tubulin, and chaperone-like the entropic contribution significantly, as activity of tubulin. bindings of both AC and DAAC were Bhattacharyya had both Bachelor’s enthalpy-driven reactions. It is the amino and Master’s degrees in Chemistry from substituent at the C-7 position in the B- Calcutta University, West Bengal. Intri- ring that converts an enthalpy-driven gued by biology, yet drawn to chemistry, reaction into an entropy-driven reaction. he went on to pursue his doctoral work – Thermodynamic data of colchicinoid– investigating the interaction of small tubulin interactions suggest that the C-7 molecules with DNA, under the guidance substituent on the B-ring of the colchici- of Umashankar Nandi (whose lab was noids studied here make additional con- first at the Indian Association for the tact(s) with the dimeric tubulin molecule. Cultivation of Science, Jadavpur and Bhattacharyya is well-known for his then at Indian Institute of Science, Ban- research on the pharmacological proper- galore). He then joined the laboratory of ties of tubulin. However, one of his sig- J. Wolff at the National Institutes of nificant contributions to tubulin research Health, Bethesda, USA as a postdoctoral was the discovery of the chaperone-like fellow. Bhattacharyya utilized his physi- activity of tubulin. Molecular chaperones cal chemistry expertise to understand are specialized classes of proteins that colchicine–tubulin interaction. Colchi- assist the folding of cellular proteins by cine is a widely used antimitotic agent protecting their structures under stress for understanding mitosis and the role of thought only to associate with microtu- conditions. Only a small number of mole- microtubules in cell division. He discov- bule-associated proteins (MAPs), also cular chaperones have been identified in ered that colchicine strongly fluoresces had an important role in the association eukaryotic cells so far and they are upon binding to tubulin. Using the de- between alpha and beta-tubulin subunits. known to assist the folding of only a velopment of colchicine fluorescence Tubulin is an important drug target. A limited subset of proteins. Therefore, it is upon tubulin binding, he elucidated sev- large number of anti-cancer drugs, such an open question how the vast majority eral interesting characteristics of colchi- as vincristine, target tubulin. Bhattacha- of proteins are folded in cells. Tubulin is cine binding to tubulin. This provided a ryya studied the interaction of several of a highly abundant multi-subunit protein method to study tubulin–colchicine inte- such drugs with tubulin, including with several hydrophobic patches and raction without using radioactivity. Even analogs of colchicine. He and his group unstructured regions. These features are today, researchers use this technique to published a detailed study of the thermo- commonly found in many chaperones. discover colchicine analogs and to un- dynamics of B-ring analogs of colchi- Bhattacharyya conceptualized the idea derstand the interactions of colchicine cine–tubulin interactions to understand that tubulin could play important roles in site agents with tubulin. He was also able the role of the C-7 substituent on the protecting cellular proteins during their to purify and polymerize membrane B-ring of the colchicinoids for tubulin– structural organization or folding. His tubulin. This discovery of the polymeri- colchicine binding. Colchicine exerts its group convincingly demonstrated that zation of the membrane tubulin was pub- antimitotic property upon binding to a mammalian tubulin stabilizes several lished in Nature. Even with all the high-affinity site on the tubulin hetero- proteins and enzymes from heat or che- prospects of a full-time research career in dimer. It is composed of a trimethoxy- mically induced aggregation. Tubulin the USA, Bhattacharyya did not deviate benzene ring (A-ring), a methoxytropone assists other cellular proteins to refold from his long-term dream of nurturing ring (C-ring) and a seven-membered ring and restore their biological activities 1940 CURRENT SCIENCE, VOL. 120, NO. 12, 25 JUNE 2021 PERSONAL NEWS during renaturation. His work also dem- chaperone activities of microtubule pro- bers in several top institutes like IITs, onstrated that tubulin interacts with the teins are exhibited in vivo, the answer of IISERs and renowned universities – substrate proteins in their unfolding or which may uncover new cellular path- would unanimously agree about his refolding intermediate states. Interestingly, ways of protein folding. inspiring demeanor. He was an excellent his work also revealed that charged Bhattacharyya’s contributions were researcher, philosopher, and most impor- C-terminal tails of tubulin play an impor- recognized by several awards and tantly an inspirational teacher. One of his tant role in imparting this function. fellowships of several Academies. He good qualities was that he truly appre- These findings could have meaningful received the Shanti Swarup Bhatnagar ciated good research, irrespective of the and far-reaching implications. Protein award in 1989 from the Council of status of the person who was doing it. He misfolding and aggregation are causal Scientific and Industrial Research encouraged young people to do good factors for numerous diseases, including (CSIR), Government of India. He was an science. He was instrumental in making Alzheimer’s, Parkinson’s and cancer. elected fellow of National Academy of Bose Institute a prominent centre of bio- Functions of several well-established Sciences, Indian Academy of Sciences, physical research. We will deeply miss molecular chaperones have been impli- Indian National Science Academy, and a Bablu, and he will always be in our cated to be closely linked to tubulin and fellow of The World Academy of memories for his patience, simplicity and microtubules. For example, heat shock Sciences. He also received the presti- pleasant personality. He is survived by protein 90 (HSP90), an abundant chape- gious Ramanna fellowship. his wife and two daughters. rone in mammalian cells, functions in Bhattacharyya contributed immensely DULAL PANDA concert with microtubules/tubulin and to the growth of protein science in India. TAPAS MANNA is trafficked along the microtubule. However, we must not fail to acknowl- GOPAL CHAKRABARTI Interestingly, later studies from the Bhat- edge his caring side and highly effective SIDDHARTHA ROY* tacharyya lab revealed that microtubule- mentorship. His peers would describe associated protein MAP2 also possesses Bablu Bhattacharyya as a kind and Bose Institute, chaperone-like activity. It will be inter- friendly person while his 24 graduate Kolkata 700 054, India esting to investigate whether or not the students – several are now faculty mem- *e-mail: [email protected] Edited by S. K. Satheesh, and printed & published by G. Madhavan for Current Science Association, Bengaluru 560 080. Typeset by WINTECS Typesetters, Bengaluru and Printed at Printek Printers, Bengaluru (Ph: 2328 7763) © 2021, Current Science Association CURRENT SCIENCE, VOL. 120, NO. 12, 25 JUNE 2021 1941.