Identifying novel sensory molecules and mechanisms in nematodes and mammals. (360G-Wellcome-103784_Z_14_Z)

£1,449,590

Despite many years of study, the molecular mechanisms underlying several humansenses, in particular hearing, touch, and sour and salt taste, remain poorly understood. Each of these processes relies on ionotropic receptors that are directly gated by the sensory stimulus; however, the mechanisms underlying this gating, and in many cases even the identities of the the relevant receptor molecules, remain unknown. Recently, work from our lab and others has implicated members of the TMC family of putative ion channels as sensory receptors for taste and hearing[1,2]. In the planned research, we will characterize the in vivo roles and functional properties of worm and mammalianTMCs and determine how they respond to sensory stimuli. Since mammalian sensory receptors often retain functionality when heterologously expressed across phyla[2,3], we will use the genetic tractability of C. elegans to dissect functional domains of mouse and worm TMCs in an in vivo context. In addition, since known families of ionotropic sensory receptors are largely conserved in the worm[4], we expect that novel receptors with conserved roles in mammals can identified by worm genetics. We will therefore screen for novel ionotropic sensory receptors by highthroughput phenotyping of C. elegans mutants. Specific aims include: 1. Characterize the functional properties of mammalian and worm TMC proteins by heterologous expression in C. elegans neurons. 2. Investigate the relationship between TMC protein structure and function through analysis of chimeras and mutant proteins. 3. Using the information from heterologous expression studies, study the in vivo functions of mouse TMCs in knockout animals. 4. Identify novel sensory receptors by high-throughput phenotyping of C. elegans knockout strains.

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Grant Details

Amount Awarded 1449590
Applicant Surname Schafer
Approval Committee Science Interview Panel
Award Date 2014-04-01T00:00:00+00:00
Financial Year 2013/14
Grant Programme: Title Investigator Award in Science
Internal ID 103784/Z/14/Z
Lead Applicant Dr William Schafer
Partnership Value 1449590
Planned Dates: End Date 2022-06-30T00:00:00+00:00
Planned Dates: Start Date 2014-07-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region South West