{"id":68,"date":"2020-09-25T18:18:15","date_gmt":"2020-09-25T18:18:15","guid":{"rendered":"https:\/\/be.iisc.ac.in\/~mkjolly\/?page_id=68"},"modified":"2022-10-29T07:02:49","modified_gmt":"2022-10-29T07:02:49","slug":"research","status":"publish","type":"page","link":"https:\/\/be.iisc.ac.in\/~mkjolly\/research\/","title":{"rendered":"Research"},"content":{"rendered":"\n<p class=\"wide\">Our laboratory currently focuses on following research themes:<\/p>\n\n\n\n<h5 class=\"wide wp-block-heading\"><strong>Dynamics of Epithelial-Mesenchymal Plasticity<\/strong>&nbsp;<\/h5>\n\n\n\n<div class=\"wp-block-columns wide is-layout-flex wp-container-core-columns-is-layout-9d6595d7 wp-block-columns-is-layout-flex\">\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\" style=\"flex-basis:66.66%\">\n<p>Epithelial-mesenchymal plasticity (EMP) involves reversible and dynamic cell-state transitions among epithelial, mesenchymal and hybrid epithelial\/mesenchymal (E\/M) phenotypes. We focus on identifying the molecular factors stabilizing hybrid E\/M cell-states, and characterizing the association of EMP with other axes of plasticity, such as tumor-initiation potential, immune evasion etc.&nbsp;&nbsp;<\/p>\n\n\n\n<p><a href=\"https:\/\/be.iisc.ac.in\/~mkjolly\/emppubs\/\">Selected Publications<\/a><\/p>\n<\/div>\n\n\n\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\" style=\"flex-basis:33.33%\">\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"576\" src=\"https:\/\/be.iisc.ac.in\/~mkjolly\/wp-content\/uploads\/2022\/03\/Teams-landscape-schematic-1024x576.png\" alt=\"\" class=\"wp-image-1222\" srcset=\"https:\/\/be.iisc.ac.in\/~mkjolly\/wp-content\/uploads\/2022\/03\/Teams-landscape-schematic-1024x576.png 1024w, https:\/\/be.iisc.ac.in\/~mkjolly\/wp-content\/uploads\/2022\/03\/Teams-landscape-schematic-300x169.png 300w, https:\/\/be.iisc.ac.in\/~mkjolly\/wp-content\/uploads\/2022\/03\/Teams-landscape-schematic-768x432.png 768w, https:\/\/be.iisc.ac.in\/~mkjolly\/wp-content\/uploads\/2022\/03\/Teams-landscape-schematic-1536x864.png 1536w, https:\/\/be.iisc.ac.in\/~mkjolly\/wp-content\/uploads\/2022\/03\/Teams-landscape-schematic-2048x1152.png 2048w, https:\/\/be.iisc.ac.in\/~mkjolly\/wp-content\/uploads\/2022\/03\/Teams-landscape-schematic-1568x882.png 1568w\" sizes=\"auto, (max-width: 1024px) 100vw, 1024px\" \/><\/figure>\n<\/div>\n<\/div>\n\n\n\n<h5 class=\"wide wp-block-heading\"><strong>Mechanisms underlying phenotypic heterogeneity in cell populations<\/strong>&nbsp;<\/h5>\n\n\n\n<div class=\"wp-block-columns wide is-layout-flex wp-container-core-columns-is-layout-9d6595d7 wp-block-columns-is-layout-flex\">\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\" style=\"flex-basis:66.66%\">\n<p>Stochastic cell-state transitions driven by various factors such as epigenetic modifications and asymmetric cell division can enable phenotypic heterogeneity in a genetically identical population. Such heterogeneity can enable bet-hedging, thus&nbsp; facilitating survival of a population under stress and the relapse of population upon stress withdrawal. We aim to identify different mechanisms and underlying principles enabling such phenotypic heterogeneity in diverse biological contexts.<\/p>\n\n\n\n<p><a href=\"https:\/\/be.iisc.ac.in\/~mkjolly\/mechanisms-underlying-phenotypic-heterogeneity\/\">Selected Publications<\/a>&nbsp;<\/p>\n<\/div>\n\n\n\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\" style=\"flex-basis:33.33%\">\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"399\" height=\"303\" src=\"https:\/\/be.iisc.ac.in\/~mkjolly\/wp-content\/uploads\/2022\/10\/2022-10-29_09-53-1.png\" alt=\"\" class=\"wp-image-1419\" srcset=\"https:\/\/be.iisc.ac.in\/~mkjolly\/wp-content\/uploads\/2022\/10\/2022-10-29_09-53-1.png 399w, https:\/\/be.iisc.ac.in\/~mkjolly\/wp-content\/uploads\/2022\/10\/2022-10-29_09-53-1-300x228.png 300w\" sizes=\"auto, (max-width: 399px) 100vw, 399px\" \/><\/figure>\n<\/div>\n<\/div>\n\n\n\n<h5 class=\"wide wp-block-heading\"><strong>Spatiotemporal pattern formation and collective behavior in cell populations<\/strong>&nbsp;<\/h5>\n\n\n\n<div class=\"wp-block-columns wide is-layout-flex wp-container-core-columns-is-layout-9d6595d7 wp-block-columns-is-layout-flex\">\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\" style=\"flex-basis:66.66%\">\n<p>Spatiotemporal dynamics of cellular phenotypes are often driven by their crosstalk with their microenvironment, involving cell-cell communication based feedback loops. We develop multi-scale mechanism-based models as predictive \u2018<em>in silico\u202f<\/em>co-culture\u2019 systems to elucidate the collective emergent dynamics in multiple scenarios: tissue-level patterning, collective cell migration, and tumor-stroma crosstalk.&nbsp;<\/p>\n\n\n\n<p><a href=\"https:\/\/be.iisc.ac.in\/~mkjolly\/collbehpubs\/\">Selected Publications<\/a><\/p>\n<\/div>\n\n\n\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\" style=\"flex-basis:33.33%\">\n<figure class=\"wp-block-image size-large is-resized\"><img loading=\"lazy\" decoding=\"async\" src=\"https:\/\/be.iisc.ac.in\/~mkjolly\/wp-content\/uploads\/2022\/10\/2022-10-29_09-56.png\" alt=\"\" class=\"wp-image-1417\" width=\"249\" height=\"198\" srcset=\"https:\/\/be.iisc.ac.in\/~mkjolly\/wp-content\/uploads\/2022\/10\/2022-10-29_09-56.png 465w, https:\/\/be.iisc.ac.in\/~mkjolly\/wp-content\/uploads\/2022\/10\/2022-10-29_09-56-300x239.png 300w\" sizes=\"auto, (max-width: 249px) 100vw, 249px\" \/><\/figure>\n<\/div>\n<\/div>\n\n\n\n<h5 class=\"wide wp-block-heading\"><strong>Single-cell analysis of cell-fate decisions in development and cancer<\/strong><\/h5>\n\n\n\n<div class=\"wp-block-columns wide is-layout-flex wp-container-core-columns-is-layout-9d6595d7 wp-block-columns-is-layout-flex\">\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\" style=\"flex-basis:66.66%\">\n<p>Recent single-cell high-throughput data collection has enabled tracking the trajectories of cell-fate decisions and mapping phenotypic heterogeneity in diverse biological contexts. We examine such single-cell transcriptomic data to identify branching points in decision-making, to characterize subpopulations with specific molecular and functional attributes, and to probe the dynamic evolution of different modules of co-expressed gene programs.<\/p>\n\n\n\n<p><a href=\"https:\/\/be.iisc.ac.in\/~mkjolly\/single-cell-analysis-of-cell-fate-decisions-in-cancer\/\">Selected Publications<\/a><\/p>\n<\/div>\n\n\n\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\" style=\"flex-basis:33.33%\">\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"371\" height=\"293\" src=\"https:\/\/be.iisc.ac.in\/~mkjolly\/wp-content\/uploads\/2022\/10\/2022-10-29_10-09.png\" alt=\"\" class=\"wp-image-1422\" srcset=\"https:\/\/be.iisc.ac.in\/~mkjolly\/wp-content\/uploads\/2022\/10\/2022-10-29_10-09.png 371w, https:\/\/be.iisc.ac.in\/~mkjolly\/wp-content\/uploads\/2022\/10\/2022-10-29_10-09-300x237.png 300w\" sizes=\"auto, (max-width: 371px) 100vw, 371px\" \/><\/figure>\n<\/div>\n<\/div>\n\n\n\n<h5 class=\"wide wp-block-heading\"><strong>Non-genetic mechanisms of adaptive therapy resistance<\/strong>&nbsp;<\/h5>\n\n\n\n<div class=\"wp-block-columns wide is-layout-flex wp-container-core-columns-is-layout-9d6595d7 wp-block-columns-is-layout-flex\">\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\" style=\"flex-basis:66.66%\">\n<p>Besides genetic mutations, non-genetic mechanisms such as phenotypic switching and stochastic cell-to-cell heterogeneity can enable adaptation to various stresses. For instance, drug treatment can induce a phenotypic switch in a fraction of cells to another state (Lamarckian induction). We aim to elucidate how cells adapt reversibly to various stresses, and how we can design strategies to outcompete these adaptation strategies.<\/p>\n\n\n\n<p><a href=\"https:\/\/be.iisc.ac.in\/~mkjolly\/nongenrespubs\/\">Selected Publications<\/a><\/p>\n<\/div>\n\n\n\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\" style=\"flex-basis:33.33%\">\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"404\" height=\"225\" src=\"https:\/\/be.iisc.ac.in\/~mkjolly\/wp-content\/uploads\/2022\/10\/2022-10-29_10-06.png\" alt=\"\" class=\"wp-image-1420\" srcset=\"https:\/\/be.iisc.ac.in\/~mkjolly\/wp-content\/uploads\/2022\/10\/2022-10-29_10-06.png 404w, https:\/\/be.iisc.ac.in\/~mkjolly\/wp-content\/uploads\/2022\/10\/2022-10-29_10-06-300x167.png 300w\" sizes=\"auto, (max-width: 404px) 100vw, 404px\" \/><\/figure>\n<\/div>\n<\/div>\n\n\n\n<h5 class=\"wide wp-block-heading\"><strong>Design principles of cell-fate decision-making regulatory networks<\/strong>&nbsp;<\/h5>\n\n\n\n<div class=\"wp-block-columns wide is-layout-flex wp-container-core-columns-is-layout-9d6595d7 wp-block-columns-is-layout-flex\">\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\" style=\"flex-basis:66.66%\">\n<p>Cell-fate decision-making regulatory networks often have unique features in terms of their emergent dynamics, for instance, a limited number of phenotypes despite their complex and large architecture, and balancing robustness against various perturbations with enabling cell-state switching. We are interested in decoding the topological hallmarks of biological networks, and the functional implications of those hallmarks.<\/p>\n\n\n\n<p><a href=\"https:\/\/be.iisc.ac.in\/~mkjolly\/design-principles\/\">Selected Publications<\/a><\/p>\n<\/div>\n\n\n\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\" style=\"flex-basis:33.33%\">\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"298\" height=\"264\" src=\"https:\/\/be.iisc.ac.in\/~mkjolly\/wp-content\/uploads\/2022\/10\/2022-10-29_10-08.png\" alt=\"\" class=\"wp-image-1421\"\/><\/figure>\n<\/div>\n<\/div>\n","protected":false},"excerpt":{"rendered":"<p>Our laboratory currently focuses on following research themes: Dynamics of Epithelial-Mesenchymal Plasticity&nbsp; Epithelial-mesenchymal plasticity (EMP) involves reversible and dynamic cell-state transitions among epithelial, mesenchymal and hybrid epithelial\/mesenchymal (E\/M) phenotypes. We focus on identifying the molecular factors stabilizing hybrid E\/M cell-states, and characterizing the association of EMP with other axes of plasticity, such as tumor-initiation potential,<a class=\"more-link\" href=\"https:\/\/be.iisc.ac.in\/~mkjolly\/research\/\">Continue reading <span class=\"screen-reader-text\">&#8220;Research&#8221;<\/span><\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"class_list":["post-68","page","type-page","status-publish","hentry","entry"],"jetpack_sharing_enabled":true,"_links":{"self":[{"href":"https:\/\/be.iisc.ac.in\/~mkjolly\/wp-json\/wp\/v2\/pages\/68","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/be.iisc.ac.in\/~mkjolly\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/be.iisc.ac.in\/~mkjolly\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/be.iisc.ac.in\/~mkjolly\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/be.iisc.ac.in\/~mkjolly\/wp-json\/wp\/v2\/comments?post=68"}],"version-history":[{"count":12,"href":"https:\/\/be.iisc.ac.in\/~mkjolly\/wp-json\/wp\/v2\/pages\/68\/revisions"}],"predecessor-version":[{"id":1473,"href":"https:\/\/be.iisc.ac.in\/~mkjolly\/wp-json\/wp\/v2\/pages\/68\/revisions\/1473"}],"wp:attachment":[{"href":"https:\/\/be.iisc.ac.in\/~mkjolly\/wp-json\/wp\/v2\/media?parent=68"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}