Unravelling motor protein organization on lysosomal membranes with super-resolution microscopy

This thesis first develops new methods for high-throughput and multi-color super-resolution microscopy (Chapters 2 and 3). Subsequently, I apply these methods to study the organization of motor proteins on the lysosome membrane inside cells with the purpose of determining how intracellular transport...

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Detalles Bibliográficos
Autor: Cordier, Guillaume
Tipo de recurso: tesis doctoral
Estado:Versión publicada
Fecha de publicación:2018
País:España
Institución:CBUC, CESCA
Repositorio:TDR. Tesis Doctorales en Red
OAI Identifier:oai:www.tdx.cat:10803/565415
Acceso en línea:http://hdl.handle.net/10803/565415
https://dx.doi.org/10.5821/dissertation-2117-117629
Access Level:acceso abierto
Palabra clave:Àrees temàtiques de la UPC::Física
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Descripción
Sumario:This thesis first develops new methods for high-throughput and multi-color super-resolution microscopy (Chapters 2 and 3). Subsequently, I apply these methods to study the organization of motor proteins on the lysosome membrane inside cells with the purpose of determining how intracellular transport can be regulated via motor-protein organization (Chapter 4). Chapter 1 is an Introduction to the state of the art for our knowledge in microtubule-based intracellular transport. Chapter 2 introduces the single molecule localization techniques that improve the spatial resolution of light microscopy. This chapter emphasizes the Stochastic Optical Reconstruction Microscopy (STORM) technique, which I used to study the organization of microtubule based motor proteins around lysosomes as well as the fusion and fission of mitochondria. Chapter 3 describes the development of two new techniques: (i) the use of microfluidic devices to improve the throughput of correlative live-cell and super-resolution microscopy, thus allowing to observe rare events and (ii) sequential multi-color imaging that increases the number of colors that can be imaged with STORM. Chapter 4 focuses on the biological application of sequential multicolor imaging to study the 3D organization of dynein and kinesin on lysosomal membranes. Conclusions and Future Perspectives are provided in Chapter 5.