Page 6 - CSIR-IGIB Annual Report 2020-21

SUMMARY

CSIR-Institute of Genomics and Integrative Biology has been at the forefront of deploying genomics to
understand complex human diseases. The past year has been an unprecedented experience for the
organization, being at the forefront of science in the face of a pandemic, helping with answers and
solutions to emerging patterns of the novel Coronavirus infection. Carrying on with existing research
programs that were jolted by the COVID pandemic, in addition to contributing to the need of the hour
has been the highlight of this report covering April 2020-March 2021. In this report we focus on our
scientists, who along with their teams, achieved much to be proud of as a scientific organization.

IGIB has had several flagship programs in Genomics since its inception and this year has seen our
scientists achieve greater heights in all of these. Under the leadership of Sridhar Sivasubbu, a
comprehensive resource of genetic variants from over 1000 genomes from residents of India was built.
This is a first of its kind resource from India and will enable understanding of pathogenic variants for
genetic diseases in India. Under the leadership of Vinod Scaria and Sridhar Sivasubbu, the Genomics for
Understanding Rare Diseases India Alliance Network (GUaRDIAN) program has grown over the years to
over 280 clinical collaborators. This network has benefited patients with accessible and affordable
genetic tests, and clinicians with knowledge sharing through academic medical centers. In an effort to
provide equitable use of genomic approaches to clinicians, Vinod’s lab provided training for capacity
building. He was joined in this endeavour by colleagues Sivaprakash Ramalingam, Binukumar, and
Mohamad Faruq for specific genetic diseases. Sivaprakash’s lab focuses on blood disorders and
hematological malignancies. His goal is to understand the basic biology and provide cell and gene
therapies using stem cell engineering and site-specific genome-editing. His group has established
multiple induced pluripotent stem cell (iPSC) lines from a thalassemia major and Gaucher’s disease
patient. His team is working on genome editing based correction of the involved genes; these lines are
being used for disease modeling but also hold potential for development of autologous cell replacement
therapy for these diseases. His lab is also working towards activation of fetal hemoglobin towards
treatment of beta thalassemia. Binukumar is leading the Indian Collaborative Research Network on
Wilson’s Disease (iCROWD) with the aim of understanding the genetic and clinical correlates of Wilson’s
Disease. The pilot program itself engages 45 clinicians across 20 centers of the country, aiming to
eventually impact genetic diagnosis and precision medicine for this paediatric chronic liver disease of
major prevalence in India. Wilson’s disease is a disease associated with excessive copper accumulation.
Binukumar’s team is also making efforts that would impact diagnosis and treatment of other copper
toxicity related disorders. ATP7A, a critical copper transporter is common to Menkes Disease, Occipital
horn syndrome and X-linked distal spinal muscular atrophy type 3. His lab has created a clinical genetics
resource of variants linked with these diseases. Mohammad Faruq’s lab has been running a pan-India
clinical network for providing clinical genetic services for prevalent genetic disorders with 300 single
gene tests within the GOMED (Genomics and other omics tools enabling medical decision) program.
Besides this vast network, his lab has made significant contributions with focussed efforts on genetics of
Spinocerebellar ataxia. His lab has also generated iPSC lines of several ataxias. The next step for any such
well characterized genetic disease is gene editing/correction.The development of new genome editing
tools is crucial to meet the goal of safe gene therapies. Debojyoti Chakraborty’s lab reports on
development of more efficient base editors using the FnCas9 backbone, termed enFnCas9. In parallel,
there are efforts in development of brain organoid systems from iPSCs as well as targeting of Cas9 using
nanocomplexes, two approaches towards making targeted gene therapy a reality.

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