Control of receptor trafficking as a therapeutic target in the inherited neuropathies. (360G-Wellcome-110043_Z_15_Z)
In this fellowship I plan to investigate whether mutations in hereditary neuropathy genes affect endosomal sorting of proteins and receptors to the plasma membrane of motor neurons and whether this leads to aberrant activation or inhibition of specific cellular pathways that can be targeted as potential therapies. In order to answer this question I will investigate a model of hereditary neuropathy due to mutations in BICD2. This fellowship has the following five aims. 1. To generate and charact erise a mouse embryonic stem cell-derived motor neuron model of neuropathy due to mutations in BICD2. 2. To analyse changes in the cell surface receptor landscape induced by mutations in BICD2. This will be performed using Stable Isotope Labelling of Amino-acids in Culture (SILAC) and mass spectrometry. 3. To validate in vitro the signalling pathways revealed in aim 2. 4. To validate in vivo alterations in the cell surface proteins identified and validated in aims 2 and 3. 5. To validate the changes in cell surface protein expression in human tissue. As almost all hereditary neuropathy mutations can impact on endosomal sorting and recycling to the cell surface, the techniques learnt during the fellowship may be applied to other forms of hereditary neuropathy.
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Grant Details
Amount Awarded | 412604 |
Applicant Surname | Rossor |
Approval Committee | Clinical Interview Committee |
Award Date | 2015-11-19T00:00:00+00:00 |
Financial Year | 2015/16 |
Grant Programme: Title | Postdoctoral Training Fellowship for Clinicians |
Internal ID | 110043/Z/15/Z |
Lead Applicant | Dr Alexander Rossor |
Partnership Value | 412604 |
Planned Dates: End Date | 2019-08-03T00:00:00+00:00 |
Planned Dates: Start Date | 2016-08-03T00:00:00+00:00 |
Recipient Org: Country | United Kingdom |
Region | Greater London |
Sponsor(s) | Prof Giampietro Schiavo |