Booth Id:
BEHA042
Category:
Behavioral and Social Sciences
Year:
2024
Finalist Names:
Watson, Owen (School: O'Gorman High School)
Abstract:
Addiction is a social disease that affects millions of people worldwide. It is a behavior driven by
a response to increased reward stimuli paired with an impaired ability to regulate stimulus
seeking-behavior. This is underlain by a condition in which structures and function of the
dopaminergic signaling pathways are altered while the disease’s underlying genetic mechanisms
are complex and elusive and still not completely understood. The current study continues my
previous analysis from last year that found 4 potentially druggable targets (CAMK2B, NEFL,
GABRB3, and PRKCZ) that changed in the context of addiction in both rats and humans. To
specifically investigate the single nucleotide polymorphisms of GABRB3 and PRKCZ
specifically, we conducted a bioinformatic study analyzing data from several online databases,
including gnomAD, and ClinVar. Through programs like PolyPhen2 and SIFT, we determined
the probability of SNPs to cause functional damage to the protein for all SNPs of GABRB3 and
PRKCZ. We then modeled the location of the damaging SNPs on each of the protein structures
to determine whether or not these areas could be easily accessed. Ultimately, we found that
PRKCZ and GABRB3 emerged as a high value candidates in which a variety of damaging single
nucleotide polymorphisms may occur. Furthermore, some of these variants are located on highly
accessible portions of the protein. Targeting these SNPs will augment our understanding of the
intricacies of these altered protein sequences with the potential to improve our understanding of
addicted individuals, and possibly offer effective methods of treatment.