Reference number : GC-2017-Q4-01264, amendment number : , agreement type : G, recipient legal name : Miller, Donald (University of Manitoba)|Miller, Donald (Université du Manitoba), recipient country : CA, recipient province : nan, recipient city : Manitoba, recipient postal code : nan, program name english : Engage Grants for universities, program name french : Subventions d'engagement partenarial pour les universités, program purpose english : The regulation of polyamine levels in cells is highly regulated and dependent upon both the synthesis and_x000D_
catabolism processes at work within the cell. As enzymes involved in both the synthesis (ornithine_x000D_
decarboxylase) and catabolism (spermine/spermidine actyl transferase 1; SSAT1) of polyamines are known to_x000D_
be altered under pathological conditions such as cancer, modulation of enzyme expression/activity has been_x000D_
identified as a potential therapeutic target for cancer. However, fundamental obstacles impede advancements_x000D_
in this area. As polyamine concentrations within the cell drive many important biological functions, a key_x000D_
limitation to scientific advancement of this field has been the inability to SELECTIVELY alter the expression_x000D_
of key enzymes in polyamine metabolism within DISCRETE cellular populations. A potential solution to this_x000D_
problem is the use of nanoparticle systems to delivery the desired compounds to selected cell types. By_x000D_
optimizing lipid and polymer based coatings and attaching targeting vectors to the surface of the nanoparticle it_x000D_
is possible to "tune" the nanoparticle to interact with selected cells while minimizing interactions with_x000D_
off-target cells. The objective of this research application is to design, characterize and provide initial_x000D_
proof-of-concept for targeted alteration of SSAT1 expression within a selected cell population. By optimizing_x000D_
the nanoparticle surface through lipid and polymer composition, as well as through the attachment of cell_x000D_
targeting vectors, it is hypothesized that a more effective and cell selective approach to modulation of enzyme_x000D_
expression can be achieved. Rationale for this particular enzyme and cell is based on the over-expression of_x000D_
SSAT1 observed in brain tumors and recent studies suggesting alterations in SSAT1 expression in GB could_x000D_
influence cell survival. The focus of this project is to identify survival advantages of SSAT1 in GB cells and_x000D_
develop a cellular "tuned" nanoparticle based delivery system tailored to modulate SSAT1 expression._x000D_
Ultimately the goal is to optimize nanoparticle delivery to select tumor cells while avoiding delivery to normal_x000D_
cell populations., program purpose french : The regulation of polyamine levels in cells is highly regulated and dependent upon both the synthesis and_x000D_
catabolism processes at work within the cell. As enzymes involved in both the synthesis (ornithine_x000D_
decarboxylase) and catabolism (spermine/spermidine actyl transferase 1; SSAT1) of polyamines are known to_x000D_
be altered under pathological conditions such as cancer, modulation of enzyme expression/activity has been_x000D_
identified as a potential therapeutic target for cancer. However, fundamental obstacles impede advancements_x000D_
in this area. As polyamine concentrations within the cell drive many important biological functions, a key_x000D_
limitation to scientific advancement of this field has been the inability to SELECTIVELY alter the expression_x000D_
of key enzymes in polyamine metabolism within DISCRETE cellular populations. A potential solution to this_x000D_
problem is the use of nanoparticle systems to delivery the desired compounds to selected cell types. By_x000D_
optimizing lipid and polymer based coatings and attaching targeting vectors to the surface of the nanoparticle it_x000D_
is possible to "tune" the nanoparticle to interact with selected cells while minimizing interactions with_x000D_
off-target cells. The objective of this research application is to design, characterize and provide initial_x000D_
proof-of-concept for targeted alteration of SSAT1 expression within a selected cell population. By optimizing_x000D_
the nanoparticle surface through lipid and polymer composition, as well as through the attachment of cell_x000D_
targeting vectors, it is hypothesized that a more effective and cell selective approach to modulation of enzyme_x000D_
expression can be achieved. Rationale for this particular enzyme and cell is based on the over-expression of_x000D_
SSAT1 observed in brain tumors and recent studies suggesting alterations in SSAT1 expression in GB could_x000D_
influence cell survival. The focus of this project is to identify survival advantages of SSAT1 in GB cells and_x000D_
develop a cellular "tuned" nanoparticle based delivery system tailored to modulate SSAT1 expression._x000D_
Ultimately the goal is to optimize nanoparticle delivery to select tumor cells while avoiding delivery to normal_x000D_
cell populations., agreement title english : Nanoparticle Based Cell Selective Modulation of SSAT1 Expression, agreement title french : Nanoparticle Based Cell Selective Modulation of SSAT1 Expression, agreement number : EGP, agreement value : 25000.0, agreement start date : 2018-02-07, agreement end date : nan, description english : nan, description french : nan, expected results english : nan, expected results french : nan, additional information english : Grant or Award spanning more than one fiscal year (2017-2018 to 2018-2019)., additional information french : Subvention ou bourse octroyée s'appliquant à plus d'un exercice financier (2017-2018 à 2018-2019)., owner organization : nserc-crsng, owner organization title : Natural Sciences and Engineering Research Council of Canada | Conseil de recherches en sciences naturelles et en génie du Canada