{"id":1342,"date":"2022-11-22T12:03:56","date_gmt":"2022-11-22T12:03:56","guid":{"rendered":"https:\/\/heidarsson.hi.is\/?page_id=1342"},"modified":"2022-12-08T12:45:23","modified_gmt":"2022-12-08T12:45:23","slug":"projects","status":"publish","type":"page","link":"https:\/\/heidarsson.hi.is\/?page_id=1342","title":{"rendered":"Projects"},"content":{"rendered":"\t\t
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Our Science<\/h2>\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t
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Our team<\/span> works within the field of dynamic structural biology where we have several research themes which all converge to understanding structurally complex proteins in the cell nucleus.<\/span><\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t

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\n\n\t\t\t\n\t\t\t\t\t<\/div>\n\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t
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\n\t\t\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<\/i><\/span>\n\t\t\t\t\t\t\t\t<\/i><\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\t\t\tIntrinsically disordered proteins in the nucleus <\/a>\n\t\t\t\t\t<\/div>\n\n\t\t\t\t\t

As organisms become increasingly complex, so too must they evolve a more sophisticated molecular alphabet. The recent discovery of proteins that can adopt multiple structural states is one way of addressing this complexity and it has dramatically changed our view of the protein structure-function paradigm.<\/span><\/span> Almost 40% of the human proteome is predicted to consist of <\/span><\/span>such <\/span><\/span>proteins that contain long<\/span><\/span> intrinsically<\/span><\/span> disordered regions<\/span><\/span> (IDRs)<\/span><\/span> and therefore lack a stable, well-defined three-dimensional structure. These so-called intrinsically disordered proteins (IDPs) have sometimes been referred to as belonging to the dark proteome since they are <\/span><\/span>on the edge<\/span><\/span> of traditional structural <\/span><\/span>biology<\/span><\/span> techniques. IDPs are prevalent in cellular regulation and signa<\/span><\/span>l<\/span><\/span>ling processes, and are implicated in a vast array of diseases and pathologies.\u202f<\/span><\/span> We study a wide spectrum of IDPs<\/span> in the nucleus<\/span> and aim to obtain a quantitative description of their dynamic structural ensembles to understand function.<\/span><\/span>\u00a0<\/span><\/p><\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t\t

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Transcription factors are particularly enriched in structural disorder where almost all of the ~1600 human factors contain long IDRs. Transcription factors usually have small and folded domains responsible for binding specific DNA sequences. The much longer IDRs contain the transcriptional activation domains and other regions important for binding other proteins and integrating the transcriptional machinery. Deciphering the sequence grammar of transcription factor IDRs and how it dictates structure, dynamics, and function, is one of the primary goals of our lab.<\/span>\u00a0<\/span><\/p>

A large focus in our lab is on pioneer transcription factors; these can bind and open condensed chromatin, and initiate cell identity changes. We use single-molecule approaches to map the structure and dynamics of the factors to understand their interactions with chromatin, and we monitor their effects on chromatin structure. We then use biochemistry and synthetic biology to modulate their function. Finally, we observe their functions and reprogramming abilities using methods from in vitro to living cells.<\/span>\u00a0<\/span><\/p><\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t\t

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\n\t\t\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<\/i><\/span>\n\t\t\t\t\t\t\t\t<\/i><\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\t\t\tExtremely disordered chromatin-binding proteins <\/a>\n\t\t\t\t\t<\/div>\n\n\t\t\t\t\t

Recent work has <\/span>identified <\/span>proteins<\/span> that are fully devoid of structure. These proteins have evolved to use their lack of structure for function<\/span>al activity<\/span>. One such example can be seen in a recent paper<\/a> on histone H1<\/span>. We study such extremely disordered <\/span>chromatin binding proteins and how their structural disorder relates to <\/span>regulating chromatin architecture.<\/span><\/span>\u00a0<\/span><\/p><\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t\t

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\n\t\t\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<\/i><\/span>\n\t\t\t\t\t\t\t\t<\/i><\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\t\t\tIntegrative and dynamic structural biology <\/a>\n\t\t\t\t\t<\/div>\n\n\t\t\t\t\t

Our core technique is single-molecule spectroscopy, <\/span><\/span>usually in combination with F\u00f6rster resonance energy transfer (FRET). Single-molecule FRET is a sensitive molecular ruler that allows us to measure molecular distance distributions and dynamics on a broad timescale from picoseconds to hours<\/span><\/span>, through multiparameter analysis of photon statistics<\/span><\/span>.<\/span><\/span> The experiments are performed on either freely diffusing molecules, which restricts dynamic processes to the millisecond range or on surface-immobilized molecules which allows conformational or binding kinetics to be measured on a timescale from milliseconds to minutes.<\/span> We also rely<\/span> on<\/span> ensemble methods such as<\/span> nuclear magnetic resonance (NMR) spectroscopy for atomic<\/span>–<\/span>resolution information<\/span> on protein behaviour.<\/span> When combined with molec<\/span>ular<\/span> simulations, these methods can give us a detailed view<\/span> into biomolecular structure, dynamics, and function. We strive to link molecular behaviour from in vitro to in vivo<\/span>, by ultimately using fluorescence imaging in live cells as well as genome-wide approaches to study <\/span>chromatin accessibility<\/span>.<\/span><\/span>\u00a0<\/span><\/p><\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t\t

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\n\t\t\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<\/i><\/span>\n\t\t\t\t\t\t\t\t<\/i><\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\t\t\tChromatin constructs for single-molecule studies <\/a>\n\t\t\t\t\t<\/div>\n\n\t\t\t\t\t

To study transcriptional regulation, we design and develop biochemical approaches for <\/span>producing chromatin constructs<\/span>, especially for single-molecule studies<\/span>. We are currently developing methods to site-specifically label nucleosome arrays with <\/span>defined transcription factor binding sites, to monitor chromatin structure during transcription factor binding. Most chromatin research has relied on using very stable DNA sequences that are not<\/span> normally<\/span> found in <\/span>organisms. <\/span>We<\/span> are therefore<\/span> also<\/span> devoted to<\/span> develop<\/span>ing<\/span> approaches to use <\/span>\u201enative\u201c DNA sequences for nucleosome formation<\/span>, to understand transcription under increasingly native-like conditions.<\/span><\/span>\u00a0<\/span><\/p><\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<\/div>\n\t\t","protected":false},"excerpt":{"rendered":"

Our Science Our team works within the field of dynamic structural biology where we have several research themes which all converge to understanding structurally complex proteins in the cell nucleus. Intrinsically disordered proteins in the nucleus As organisms become increasingly complex, so too must they evolve a more sophisticated molecular alphabet. The recent discovery of […]<\/p>\n","protected":false},"author":3,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"brizy_media":[],"_links":{"self":[{"href":"https:\/\/heidarsson.hi.is\/index.php?rest_route=\/wp\/v2\/pages\/1342"}],"collection":[{"href":"https:\/\/heidarsson.hi.is\/index.php?rest_route=\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/heidarsson.hi.is\/index.php?rest_route=\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/heidarsson.hi.is\/index.php?rest_route=\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/heidarsson.hi.is\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=1342"}],"version-history":[{"count":10,"href":"https:\/\/heidarsson.hi.is\/index.php?rest_route=\/wp\/v2\/pages\/1342\/revisions"}],"predecessor-version":[{"id":1478,"href":"https:\/\/heidarsson.hi.is\/index.php?rest_route=\/wp\/v2\/pages\/1342\/revisions\/1478"}],"wp:attachment":[{"href":"https:\/\/heidarsson.hi.is\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=1342"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}