Sudipto ROY   
                       
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  Sudipto ROY  
  Lab Location: #8-12

email:
sudipto@imcb.a-star.edu.sg
tel:65869744
 
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  Recent Publications  
 


D. Babu, S. Roy.
Left-right asymmetry: Cilia stir up new surprises in the node.
Open Biology 3: 130052, 2013.

S. P. Choksi, G. Lauter, P. Swoboda, S. Roy.
Switching on cilia: transcriptional networks regulating ciliogenesis.
Development 141: 1427-1441, 2014.

S. P. Choksi, D. Babu, D. Lau, X. Yu, S. Roy.
Systematic discovery of novel ciliary genes through functional genomics in the zebrafish.
Development 141: 3410-3419, 2014.

H. Lu, M. T. Toh, V. Narasimhan, S. K. Thamilselvam, S. P. Choksi, S. Roy.
A function for the Joubert syndrome protein Arl13b in ciliary membrane extension and ciliary length regulation.
Developmental Biology 397: 225-236, 2015.

V. Narasimhan, R. Hjeij, S. Vij, N. T. Loges, J. Wallmeier, C. Koerner-Rettberg, C. Werner, S. K. Thamilselvam, A. Boey, S. P. Choksi, P. Pennekamp, S. Roy, H. Omran.
Mutations in CCDC11, which encodes a coiled-coil containing ciliary protein, causes situs inversus due to dysmotility of monocilia in the left-right organizer.
Human Mutation 36: 307-318, 2015.

V. Narasimhan, S. Roy. 
Cilia: organelles at heart of heart disease.
Current Biology 25: R559-562, 2015.

F. Zhou, S. Roy. 
SnapShot: Motile cilia.
Cell 162: 224, 2015.

P. Boyd, V. T. Cunliffe, S. Roy, J. Wood. 
Sonic hedgehog functions upstream of disrupted-in-schizophrenia 1 (disc1): Implications for mental illness.
Biology Open 4: 1336-1343, 2015.

F. Zhou, V. Narasimhan, M.  Shboul, Y. L. Chong, B. Reversade, S. Roy.
Gmnc is a master regulator of the multiciliated cell differentiation program.
Current Biology 25: 3267-3273, 2015.

 
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  Sudipto ROY


Sudipto Roy was educated at some of the most distinguished institutions in India. He graduated in 1991 with a first class first in zoology (honors) from Presidency College in Calcutta, and again secured the first position during his M.Sc. studies at the Jawaharlal Nehru University, New Delhi, in 1993. He then moved to the National Centre for Biological Sciences in Bangalore, where he obtained a Ph.D. in developmental genetics, studying the cellular and genetic basis of muscle and neuronal development in the fruit fly, Drosophila, with K. VijayRaghavan. During this period, he travelled to Brandeis University in the US and to Cambridge University, England, as a visiting graduate student. He began post-doctoral studies at the Centre for Developmental and Biomedical Genetics at the University of Sheffield, England, in 1998, where he initiated research into vertebrate development using the zebrafish embryo in the laboratory of Philip Ingham. In 2002, he joined the Institute of Molecular and Cell Biology in Singapore as a Young Investigator, and was a Principal Investigator (Assistant Professor) from 2003-2008. Dr. Roy is currently a Senior Principal Investigator and is an adjunct Associate Professor with the Department of Biological Sciences and the Department of Pediatrics of the National University of Singapore. He has been the recipient of several awards and fellowships from international organizations that include the Company of Biologists, the Wellcome Trust, the Human Frontiers Science Program (HFSP) and the European Molecular Biology Organization (EMBO). He has been honored with the prestigious Indian National Science Academy Young Scientist Medal by the President of India (2002), the STAR Employee Award from the Agency for Science Technology and Research of Singapore (2012), and more recently, the first distinguished alumnus award from the National Centre for Biological Sciences (2016). Over the years, he and his colleagues have made important contributions to our understanding of many aspects of developmental biology that include how hox genes regulate muscle patterning, the discovery of blimp1 as a selector gene for slow-twitch muscle, the genetics of myoblast fusion, the identification of Kif7 and Dzip1 as ciliary proteins in the Hedgehog pathway and the master regulatory roles of the Foxj1 and Gmnc transcription factors in programming the biogenesis of motile cilia. He also serves on the editorial board of the Journal of Genetics, Biology Open, PLoS One and oversees the functioning of the IMCB zebrafish facility and the electron microscopy suite.

     
 

Cilia and Ciliopathies

 


Cilia and flagella are hair-like filamentous organelles that have been conserved evolutionarily in the eukaryotes. Our high school lectures have taught us how protozoans, like Paramecium, use beating cilia to swim around in water. We have also learnt that certain tissues in our own bodies have motile cilia. For instance, motile cilia that line the length of our respiratory tract beat to clear mucus that entangles pathogens and pollutants which enter through the nose as we breathe. Cilia also perform sensory functions. Besides locomotion, cilia in the protozoans are used for phototactic and chemotactic behavior. In the metazoans, many sense organs have cilia that have lost the motility apparatus and have become dedicated sensory organelles. Photoreceptors in the eye and olfactory neurons in the nose have such highly specialized sensory cilia. Several decades ago it was discovered that in the vertebrates, not just the sense organs, but almost every cell of the body differentiates a single immotile cilium at the end of cell division or after differentiation. Although regarded as vestigial structures for a long time, it has now become apparent that these so called primary cilia also function as hubs for a large number of signaling pathways that operate during embryonic development and in adult physiology.

     
     
   
The filamentous part of the cilium that extends out of the cell surface is called the axoneme, and consists of a microtubule scaffold enveloped by an extension of the cell membrane. The axoneme remains anchored to the basal body that is derived from the mother centriole. The ultrastructure of cilia can vary, depending on their function. Sensory or primary cilia typically have 9 radially arranged microtubule doublets (9+0 pattern), whereas the motile cilia, in addition, usually have a central pair of singlet microtubules (9+2 pattern). Furthermore, the motile cilia have dynein arms on the peripheral microtubule doublets that confer motility. A wide spectrum of human diseases arises from defects in cilia formation and function. Abnormalities of the primary cilia result in syndromes like Alstrom, Bardet-Biedl, Joubert, Meckel-Gruber, Senior-Loken as well as other conditions like polycystic kidney disease and nephronophthisis. Symptoms of these diseases range from orofacial deformities, abnormalities in limb development, retinal degeneration, as well as formation of kidney cysts. On the other hand, dysfunctional motile cilia can also instigate pathological consequences, exemplified by disorders such as Primary Ciliary Dyskinesia (PCD) and Kartagener syndrome. Individuals afflicted with PCD have immotile or dyskinetic cilia and flagella, and, consequently, defective mucociliary clearance, chronic pulmonary infections and infertility (in males). Many individuals with PCD show perturbations in left-right asymmetry of internal organs (Kartagener syndrome) that ensue from defective motility of cilia in the embryonic node. Fluid flow over the node, driven by rotary beating of motile cilia, is thought to trigger a signaling cascade that breaks the initial bilateral symmetry of the embryo. Thus, elucidating the developmental basis of ciliary biogenesis will not only further our understanding of key events in embryogenesis , but will also broaden our insights into the etiology of ciliopathies. Such a profound impact of the cilium on human health is indeed the motivation behind the intensive research being carried out world-wide on the biology of this organelle.
We are using genetic and cell biological analysis in the zebrafish embryo and mammalian cells to understand the regulatory pathways that direct ciliogenesis, the activities of many of the individual proteins that constitute structural and functional components of cilia, and how different developmental and physiological pathways use cilia as platforms for their signaling activity. Over the past few years, we have made important contributions to the field of ciliary biology, some of which are highlighted below. In 2004, through positional cloning in zebrafish, we identified a new zinc finger and coiled-coil containing protein, Dzip1, that we recently showed to be associated with the ciliary basal bodies. Dzip1 is required for axonemal differentiation, and the role of this protein in ciliary pathology is currently being investigated. The following year we published our work on the identification of Kif7, the first vertebrate orthologue of Costal2, a kinesin-like protein in Drosophila involved in Hedgehog signaling. Several groups have followed up on our findings and have now shown that Kif7 is a ciliary kinesin that is mutated in fetal hydrolethalus, acrocallosal and Joubert syndromes. In a seminal piece of work published in 2008, our group made the pioneering discovery that the forkhead transcription factor FoxJ1 is the master regulator of motile cilia biogenesis. We found that FoxJ1 is not just necessary for motile cilia to form, but is also sufficient to reprogram cells that normally do not make motile cilia to ectopically differentiate this organelle. Inspired by this striking attribute of FoxJ1, we now have undertaken a genome-wide search for the targets genes that are regulated by this transcription factor. We have found that the expression of more than 600 genes is activated by FoxJ1 during ciliogenesis, giving us the first global view of the vertebrate ciliary transcriptome. Many of these genes encode previously described components of the ciliary apparatus; more importantly, the list is replete with many completely novel genes that have not been implicated in cilia formation or function in previous studies. Our current efforts are directed at understanding the contributions of the proteins encoded by these genes in cilium differentiation and function, and their possible roles in the pathogenesis of ciliopathies.
     
   



Video link to Dr Roy's lecture on Cilia in Development and Disease