Difference between revisions of "Team:Waterloo"

Human neurodegenerative diseases (NDDs) like Creutzfeldt-Jakob, Alzheimer’s, and Parkinson’s disease are associated with multiple metabolic complications in neurons. To name a known few, the metabolism of cholesterol, copper, iron, heme, NAD+, and some neurotransmitters have all been shown to be affected by prion proteins affiliated with these NDDs1,2,3,4,5. It is important to continue studying the metabolic implications of NDDs to further elucidate their pathological mechanisms. For diseases like Alzheimer’s, years of work have been put in, yet treatment and therapy are only beginning to progress more rapidly. We hope to contribute to this field by providing a synthetic biology approach that enables an alternative method for metabolic studies in neurons affected by prion proteins.

This year, we’ve designed a negative feedback loop using a novel regulatory element capable of overexpressing or repressing target proteins upon transitioning from a neutral state to a prion state. As a proof-of-concept, we use the Sup35 prion protein associated with the [psi-] (healthy) / [PSI+] (disease-like) state of Saccharomyces cerevisiae cells. We use read-through of a premature stop codon in fusions with Hsp104 or dCas9 to respectively overexpress or repress Hsp104. Both overexpression and repression of Hsp104, through different mechanisms outlined here, cures the [PSI+] state – from priON to OFF.