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RNA signatures in cell-fate decisions
Our research aims to uncover novel factors that modulate cellular pathways, particularly embryonic stem cell-fate and neuronal migration using cerebral organoid models.
We are engaged in developing potent CRISPR-Cas9-based tools to dissect out genetic circuitry of ESCs and develop point-of-care diagnostics along with effective and cheaper gene editing tools for the treatment of diseases like Sickle Cell Anemia.
We are based at the CSIR-Institute of genomics & integrative biology in new Delhi, India
Embryonic Stem Cells
Embryonic stem (ES) cells originate from the inner cell mass of the blastocyst of female mammals. As one of the first cells formed in the body, they possess the power of pluripotency, a term that denotes the capability to give rise to virtually any other cell or tissue type in the body, be it a cardiomyocyte or a neuron. Hence ES cells offer a lot of promise for therapeutic purposes where they can potentially be used to generate a faulty or a defective organ if the right cues are given. This process is termed as lineage commitment. However, defining the lineage of an embryonic stem cell depends on the correct knowledge about the factors that control these processes so that these can be tweaked based on our needs. In our lab, we study some of these factors and try to better understand their roles during development.
Probably no other genome engineering technology has made such an impact on scientific progress as CRISPR-Cas9. The applicability of this system has extended from gene discovery to crop improvement, from studying disease models to identifying drug targets. Owing to its potential to become a gene therapy agent (an application where the system can be used to correct a faulty or defective gene in a diseased individual and offer a curative strategy) a lot of current research is aimed at increasing the specificity and efficiency of its action. Together with the lab of Souvik Maiti, we plan to tackle this using chemical biology approaches and develop alternate and potent DNA and RNA editing agents.
Our lab works with cerebral organoids (or ‘mini brains’) that are cultured using pluripotent stem cells. These tiny 'organs on a dish' recapitulate the developmental plasticity of the actual mammalian brain and is a great model for studying development, discovering novel drug molecules, and modelling diseases. When grown from patient specific induced pluripotent stem cells (iPSCs), cerebral organoids have a lot of potential in personalized medicine and therapy. Along with the labs of Souvik Maiti and Beena Pillai, we are involved in testing small molecules in the growth and proliferation of mouse organoids and are using genome editing to make/correct neurodegenerative disease models.
We are presently using these models for studying disease pathogenesis of Megalencephalic Leukoencephalopathy (MLC) and Spinocerebellar Ataxia (SCA) Type 17 to create better disease models, which would better simulate the disease characteristics seen in humans and thereafter apply CRISPR-Cas based gene editing for potential treatment of these diseases.
Another exciting area of research in the lab is to study the role of lnRNAs and their regulation during early neuronal development using cortical spheroids.
Long non-coding RNAs
Long noncoding RNAs (lncRNAs) are a class of RNAs that do not produce a functional protein product. Although there are a large number of them inside the cell, they are lowly expressed and are generally poorly understood in terms of function. In recent years, owing to the development of better strategies to identify and study them, lncRNAs have been implicated in a variety of different cellular pathways including disease progression. We are interested in studying functional lncRNAs that are implicated in certain types of cancer in the Indian population and develop strategies to utilize them as molecular biomarkers for early diagnosis and better prognostics.
Genome Editing Workshop, IGIB
DC Lab organised a Hands-on-Training Workshop on "Genome Editing via CRISPR-Cas9" at CSIR-IGIB.
ACBICON Conference, New Delhi
PhD students from DC lab presented their research work at the ACBICON conference at ICAR, New Delhi.
EMBL Symposium, Heidelberg
PhD student Meghali Aich presented her research work on "Regulated interaction of Panct1 with TOBF1 modulates mouse embryonic stem cell fate by regulating alternative splicing" at the EMBL Symposium in Heidelberg.
EMBO Workshop, Singapore
PhD student Rhythm Phutela presented her research work on "Molecular Dissection of DNA targeting properties of FnCas9 for disease detection and correction" at the EMBO Workshop on DNA Damage Response, Immunity and Ageing in Singapore.
FGE Meeting, Seoul
Dr. Debojyoti Chakraborty presented with Prof. David Liu, Broad Institute, Harvard at the Frontiers in Genome Engineering 2022 Meeting (FGE 2022) in Seoul, South Korea. The topic was “Reading and writing the genome with precision”
WellCome Science Connect Conference
Ph.D student Rhythm Phutela presented her research at the Wellcome Connecting Science Conference- CRISPR and Beyond on the topic “Dissecting the molecular repair dynamics induced by Cas9 DNA cleavage”.
Bardoli Clinical Trials
Dr. Debojyoti Chakraborty and Dr. Souvik Maiti along with AIIMS physicians Dr. Rishi Dhawan and Dr. Ganesh Kumar visited Shishudeep Multispeciality Hospital, Bardoli for discussions regarding potential clinical trials.
EMBO Meeting, Spain
PhD student Sundaram Acharya presented at the EMBO Conference in Spain on the “Engineered PAM-flexible FnCas9 variants with enhanced activity for robust and specific genome editing and diagnostics”. He was awarded the EMBO Travel grant and also received travel support from Sun Pharma.
Exchange Program, Monash University
Ph.D student Riya Rauthan from DC Lab has joined as a visiting scholar at Monash Biomedicine Discovery Institute at Monash University, Australia. She will be carrying out collaborative work on microscopy of organoids in Dr. Senthil Arumugam's lab.
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