Difference between revisions of "Team:Lethbridge/Model"

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<h1>MODEL</h1>
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<p>While VLPs will be useful components of VINCEnT, we wanted to focus on development of a novel non-immunogenic PNC with RNA packaging capabilities. Such a tool could enable simpler transfection of mammalian cell lines for fellow iGEMers and other researchers.
  
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To do this, we identified the Rattus norvegicus Arc protein as a candidate for modelling a minimal packaging protein. Arc is an activity-regulated cytoskeletal-associated protein that has recently been recognized as a repurposed Ty3/Gypsy retrotransposon. A bi-lobar domain within Arc has significant homology to Gag proteins, which are the major capsid proteins of many viruses including Human Immunodeficiency Virus type 1 (HIV-1), Rous-Sarcoma Virus (RSV), and Bovine Leukemia Virus (BLV). In response to synaptic activity in neurons, Arc proteins self-assemble via this Gag domain (similar to the related viral particles) to encapsulate Arc mRNA and shuttle it to neighbouring cells (Pastuzyn et al., 2018; Ashley et al., 2018).
  
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To ensure we would not retain any native Arc functionality that might impact cellular activity, we designed a “minimal” Arc Gag protein based on homology with other known Gag domains. We used template-based structural predictions to model this minimal Arc Gag and its predicted assembly into higher-order structures.
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Revision as of 16:11, 13 October 2018



MODEL



While VLPs will be useful components of VINCEnT, we wanted to focus on development of a novel non-immunogenic PNC with RNA packaging capabilities. Such a tool could enable simpler transfection of mammalian cell lines for fellow iGEMers and other researchers. To do this, we identified the Rattus norvegicus Arc protein as a candidate for modelling a minimal packaging protein. Arc is an activity-regulated cytoskeletal-associated protein that has recently been recognized as a repurposed Ty3/Gypsy retrotransposon. A bi-lobar domain within Arc has significant homology to Gag proteins, which are the major capsid proteins of many viruses including Human Immunodeficiency Virus type 1 (HIV-1), Rous-Sarcoma Virus (RSV), and Bovine Leukemia Virus (BLV). In response to synaptic activity in neurons, Arc proteins self-assemble via this Gag domain (similar to the related viral particles) to encapsulate Arc mRNA and shuttle it to neighbouring cells (Pastuzyn et al., 2018; Ashley et al., 2018). To ensure we would not retain any native Arc functionality that might impact cellular activity, we designed a “minimal” Arc Gag protein based on homology with other known Gag domains. We used template-based structural predictions to model this minimal Arc Gag and its predicted assembly into higher-order structures.