Mapping the Conformational Dynamics of E-selectin upon Interaction with its Ligands

Handle URI:
http://hdl.handle.net/10754/292320
Title:
Mapping the Conformational Dynamics of E-selectin upon Interaction with its Ligands
Authors:
Aleisa, Fajr A
Abstract:
Selectins are key adhesion molecules responsible for initiating a multistep process that leads a cell out of the blood circulation and into a tissue or organ. The adhesion of cells (expressing ligands) to the endothelium (expressing the selectin i.e.,E-selectin) occurs through spatio-temporally regulated interactions that are mediated by multiple intra- and inter-cellular components. The mechanism of cell adhesion is investigated primarily using ensemble-based experiments, which provides indirect information about how individual molecules work in such a complex system. Recent developments in single-molecule (SM) fluorescence detection allow for the visualization of individual molecules with a good spatio-temporal resolution nanometer spatial resolution and millisecond time resolution). Furthermore, advanced SM fluorescence techniques such as Förster Resonance Energy Transfer (FRET) and super-resolution microscopy provide unique opportunities to obtain information about nanometer-scale conformational dynamics of proteins as well as nano-scale architectures of biological samples. Therefore, the state-of-the-art SM techniques are powerful tools for investigating complex biological system such as the mechanism of cell adhesion. In this project, several constructs of fluorescently labeled E-selectin will be used to study the conformational dynamics of E-selectin binding to its ligand(s) using SM-FRET and combination of SM-FRET and force microscopy. These studies will be beneficial to fully understand the mechanistic details of cell adhesion and migration of cells using the established model system of hematopoietic stem cells (HSCs) adhesion to the selectin expressing endothelial cells (such as the E-selectin expressing endothelial cells in the bone marrow).
Advisors:
Merzaban, Jasmeen ( 0000-0002-7276-2907 )
Committee Member:
Gadhoum, Samah Z.; Gehring, Christoph A ( 0000-0003-4355-4591 )
KAUST Department:
Biological and Environmental Sciences and Engineering (BESE) Division
Program:
Bioscience
Issue Date:
15-May-2013
Type:
Thesis
Appears in Collections:
Bioscience Program; Theses; Biological and Environmental Sciences and Engineering (BESE) Division

Full metadata record

DC FieldValue Language
dc.contributor.advisorMerzaban, Jasmeenen
dc.contributor.authorAleisa, Fajr Aen
dc.date.accessioned2013-05-18T07:20:46Z-
dc.date.available2013-05-18T07:20:46Z-
dc.date.issued2013-05-15en
dc.identifier.urihttp://hdl.handle.net/10754/292320en
dc.description.abstractSelectins are key adhesion molecules responsible for initiating a multistep process that leads a cell out of the blood circulation and into a tissue or organ. The adhesion of cells (expressing ligands) to the endothelium (expressing the selectin i.e.,E-selectin) occurs through spatio-temporally regulated interactions that are mediated by multiple intra- and inter-cellular components. The mechanism of cell adhesion is investigated primarily using ensemble-based experiments, which provides indirect information about how individual molecules work in such a complex system. Recent developments in single-molecule (SM) fluorescence detection allow for the visualization of individual molecules with a good spatio-temporal resolution nanometer spatial resolution and millisecond time resolution). Furthermore, advanced SM fluorescence techniques such as Förster Resonance Energy Transfer (FRET) and super-resolution microscopy provide unique opportunities to obtain information about nanometer-scale conformational dynamics of proteins as well as nano-scale architectures of biological samples. Therefore, the state-of-the-art SM techniques are powerful tools for investigating complex biological system such as the mechanism of cell adhesion. In this project, several constructs of fluorescently labeled E-selectin will be used to study the conformational dynamics of E-selectin binding to its ligand(s) using SM-FRET and combination of SM-FRET and force microscopy. These studies will be beneficial to fully understand the mechanistic details of cell adhesion and migration of cells using the established model system of hematopoietic stem cells (HSCs) adhesion to the selectin expressing endothelial cells (such as the E-selectin expressing endothelial cells in the bone marrow).en
dc.language.isoenen
dc.subjectE-Selectinen
dc.subjectcloningen
dc.subjectSf9 cellsen
dc.subjectCHO-Kl cellsen
dc.subjectHermatopoietic stem cells (HSC)en
dc.subjectForster resonance energy transfer (FRET)en
dc.titleMapping the Conformational Dynamics of E-selectin upon Interaction with its Ligandsen
dc.typeThesisen
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Divisionen
thesis.degree.grantorKing Abdullah University of Science and Technologyen_GB
dc.contributor.committeememberGadhoum, Samah Z.en
dc.contributor.committeememberGehring, Christoph Aen
thesis.degree.disciplineBioscienceen
thesis.degree.nameMaster of Scienceen
dc.person.id118470en
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