As an institution, inStem is entering a new phase as it completes its sixth year, a steady state with its six themes and a clinical translational unit. The sudden burst of birth and growth have had their trials and tribulations as would any new institution, and inStem appears to be wearing its growing pains rather well. The movement towards becoming a full-fledged and autonomous unit of the DBT is a slow and steady process, requiring a firm grip on a number of parameters, including the vagaries of the El Nino as it alters the course of the monsoon over the Bay of Bengal. However, there is comfort in the knowledge that there is now a clear path for moving inStem into an institutional mode very soon. The debt to the campus and its excellent facilities can only be paid in the generation of excellent science.

Last year we asked a question: Does the culture of ‘collaborative inquiry’ allow inStem to tackle major, complex, scientific problems that are difficult to pursue in single investigator laboratories? There are several measures of success that have been suggested. One is the tangible output that we generate, another is the collaborative culture that must evolve, and the third is the ability to attract people who wish to work in such an environment.

While scientific output has achieved a steady stream, it is also becoming very clear that the function of individual themes have a spectrum of operational features with each one displaying unique characteristics. For instance, the Centre for Chemical Biology and Therapeutics (CCBT) is gearing up very well with the establishment of an extraordinarly high quality programme in uncovering new molecules targeting phospho-peptide protein interactions, in a close knit team effort that will reach out to its environs after creating scientific assets for the community. The Centre for Brain Development and Repair (CBDR), has established a platform programme (Centre for Synaptic Neuropathies) for studying the neurophysiological aspects of stem cells taken from patients carrying autism spectrum disorders (ASDs). Again, in a very exciting beginning, this group has carried out electrophysiological characterizations of specific perturbations in neurons generated from ASD patient-derived iPSCs. The Cardiovascular Biology and Disease (CCBD) theme is in an exciting phase of expanding its original mandate with the recruitment of structural biologist Minhaj Sirajuddin and Dhandhapany Perundurai, a human geneticist interested in studying perturbations in signalling pathways in paediatric cardiomyopathies. Another development for this team is the engagement of Sivaramakrishnan (University of Minnesota) as a named collaborator, reflecting the true capacity of a theme to build an interdisciplinary programme focussing on all the scales involved in cardiomyopathy. The nascent Regulation of Cell Fate (RCF) programme celebrates its formation with an award of a Centre of Excellence grant (from the DBT). The award is a recognition of how a set of investigators can come together to jointly address an important question in basic biology. The Centre for Inflammation and Tissue Homeostasis (CITH) theme has consolidated its efforts with Colin Jamora’s view of homeostasis coinciding with Srikala Raghavan’s exciting discovery of the mechanisms of sterile inflammation in a mouse model of aberrations in skin development and epigenetics by engaging with Shravanti Rampalli- Deshpande within the theme. The Technologies for Advancement of Science (TAS) theme continues its exploration of new tools and technologies with exciting applications of an addressable chemical scaffold as a drug delivery device, making its way into clinical trials in large mammals. Along with the Structural Biology group at NCBS, Rams is steering the development of one of India’s first Cryo-EM installations and we hope this will be realized in the next year.
 


S MAYOR
Director, inStem

The clinical translational unit run at the Christian Medical College (CMC) led by Alok Srivastava, the Centre for Stem Cell Research (CSCR) is another endeavour where clinical translation is being honed into three main areas of focus. Two are founded on core interests in gene therapy for hemophilia (based on the recognition of underutilized AAV vectors in collaboration with Amit Nathwani at UCL, London, UK and Arun Srivastava at UFL, Gainesville, USA) and thalassemia (based on lenti viral vectors in collaboration with Trent Spencer at Emory University, USA).The third is on a musculoskeletal regeneration programme led by Vrisha Madhuri. The outcome of this latter focus is currently undergoing clinical trials in articular and physeal cartilage replacement, along with bone and muscle regeneration. The major challenge at CSCR for its programmes is to ensure clear translational goals for each activity and team. The procedures that will help achieve this are in the process of being developed with a lot of help from Mahendra Rao, the Chair of the Scientific Advisory Board of CSCR.

The engagement of Azim Surani, Jawaharlal Nehru Fellow and member of our Scientific Advisory Board in activities at inStem has been extremly productive due to his extraordinary capacity to mentor our junior and not-so-junior colleagues. We are grateful for the fellowship as well as Azim’s perseverance. We welcome the involvement of Mahendra Rao, a long-time associate of our campus who is also a member of inStem’s scientific advisory board. He is our latest Collaborative Science Chair, and is putting in place a major programme in stem cell derivation and utilization in a joint programme with the National Institute of Mental Health and Neuroscience (NIMHANS), NCBS and inStem. In this programme, we are engaging with clinicians to obtain iPSC lines from a pilot-scale set of patient cohorts from five different clinics who have been carefully chosen by NIMHANS clinicians and colleagues from NCBS (including Sanjeev Jain, adjunct professor at NCBS and inStem and Raghu Padinjat). Mahendra Rao will be associated with the CBDR theme at inStem.

I cannot adequately emphasize the excellent catalytic support from the Shanta Wadhwani Foundation for the CBDR and CCBD themes, and our heartfelt thanks to Romesh Wadhwani and Ajay Kela for the faith they have reposed in our endeavours. This type of funding has allowed us to take risks and recruit new people and initiate new activities. Our efforts to attract enlightened private funding over the next year, will be redoubled.

Of course our major challenges lie ahead at inStem in the ever present concern of developing a unique institutional culture as a thematically driven collaborative environment. This is vital for taking on scientific questions that a single laboratory will find difficult to take on. This is the identity that we hope inStem will grow up to embody, distinguishing itself from all other institutes for basic biology. We continue to leverage the advantages of the collective might of the three institutes of the Bangalore Biocluster (NCBS, inStem and CCAMP) to come together, and chart a bright new future.