Emergence of Cellular Heterogeneity in Expression of an Oncofetal Protein

Talk give at 34^th Annual Convention of Indian Association for Cancer Research (<b>IACR2015</b>), 19^th– 21^st February 2015 Jaipur. <div><b><br></b><div><b>Abstract: </b>It is now well established that cells in a tumor are heterogeneous. Such heterogeneity originates for various reasons, including accumulation of random mutations. It is commonly assumed that a population of genetically identical, clonally-derived, cells will be homogenous and all the cells in that population would behave similarly. However, that is not true. Like many other cellular processes, expression of a gene is stochastic. Such stochasticity leads to non-genetic cellular heterogeneity in gene expression. Heterogeneity in gene expression often leads to different phenotypic states within a population of cells. Design of the transcriptional circuit affects the heterogeneity. A positive feedback, in a transcriptional circuit, amplifies noise in gene expression and often triggers emergence of two subpopulations. Here, in this work we show that transcription of an oncofetal protein human Cripto-1 (CR-1) is regulated through an autoregulatory positive feedback. We characterize this feedback using biochemical tools. We further show that induction of this circuit leads to spontaneous emergence of two sub-populations, having higher and lower expression of CR-1. Such heterogeneity in CR-1 expression is observed in clinical samples and in multiple cancer cell lines. We use both experimental and mathematical simulation to understand the phenomenon. We have observed that MDR-1, a drug resistance gene, is also co-induced in the subpopulation having higher expression of CR-1. Our work emphasizes involvement of  CR-1 in the phenotypic diversification of cancer cells and spontaneous emergence of probable drug resistant subpopulation.</div><p> <br></p></div

Is it all in your gene?

This is a power point presentation used for a talk to School children (11th standard) on genes, genetics and us. It focuses mostly on the old debate of nature vs nurture and deals with the question how much of us is determined by Genes only

Organizing Principles in Biology

This is a talk delivered at the Department of Physics, IIT Guwahati in March 2015. It discusses issues of self-organization, network and network behavior in biology

Molecular Signaling Network of Cripto-1

<p>This is a presentation on identification of an incoherent feed-forward loop in Cripto-1 signaling. Cripto-1 is an oncofetal protein. We have shown that Cripto-1 can activate both PI3K pathway as well increases PTEN. This creats a self-regulatory feedforward loop. This presentation is based on the paper: Cancer Lett. 2012 318(2): 189-98 [PMID: 22182448]. This presentation was made at a meeting at B. Borooah Cancer Institute (BBCI), Guwahati, India in 2012</p

Mathematical Modeling of Signal Transduction Pathways

<p>A general lecture on mathematical modeling for understanding dynamics of cell signaling pathways. Presented at the workshop Advances in Computational Biology and Computer Aided Drug Design at Indian Institute of Technology Guwahati, on 24th June 2015.</p

Old Protein, New Tricks

<p>This is a presentation on use of the recombinant receptor binding-domain of Diphtheria Toxin for targeted drug delivary. It shows that Curcumin binds to this recombinant protetin and gets delivered to cells expressing the recptor for Diphtheria toxin. The receptor for Diphtheria toxin is a membrane bound growth factor that is overexpressed in various cancers. This presentation is based on our publication: Mol Pharm. 2013 11(1): 208-17 [PMID: 24224661]. It was presented at the Jadavpur University, Kolkata in August 2014.  </p