Cargo transport by dynein/dynactin (360G-Wellcome-210711_Z_18_Z)
Eukaryotic cells rely on motor proteins for their internal organization and movement. I want to ask how one cytoplasmic dynein, together with its cofactor dynactin, can be responsible for almost all of the minus-end directed microtubule transport in our cells. My group will focus on endosome transport as a model system to understand which adaptor proteins are needed to link dynein to cargos. We will use in vitro reconstitution and cryo-EM to ask how different candidate adaptors interact with dynein/dynactin. We will also use structural approaches to understand how the different adaptors are themselves linked to membrane surfaces. To complement this approach we will purify endosomes and use cross-linking and mass spectrometry to search for any missing components required for dynein binding. We will take advantage of recent advances in cryo-electron tomography (cryoET) to ask how dynein/dynactin complexes and their associated connections are arranged on endosomes, both in vitro and in axons of cultured neurons. These studies will uncover the principles governing dynein/dynactin interactions with cargos and will allow us to ask how the process can be hijacked by pathogens such as herpes or rabies viruses.
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Grant Details
Amount Awarded | 1450105 |
Applicant Surname | Carter |
Approval Committee | Science Interview Panel |
Award Date | 2018-04-10T00:00:00+00:00 |
Financial Year | 2017/18 |
Grant Programme: Title | Investigator Award in Science |
Internal ID | 210711/Z/18/Z |
Lead Applicant | Dr Andrew Carter |
Partnership Value | 1450105 |
Planned Dates: End Date | 2024-09-01T00:00:00+00:00 |
Planned Dates: Start Date | 2018-09-01T00:00:00+00:00 |
Recipient Org: Country | United Kingdom |
Region | South West |