Pathways from epigenomics and glycobiology towards novel biomarkers of addiction and its radical cure
School of Medical and Health Sciences
The recent demonstration that addiction-relevant neuronal ensembles defined by known master transcription factors and their connectome is networked throughout mesocorticolimbic reward circuits and resonates harmonically at known frequencies implies that single-cell pan-omics techniques can improve our understanding of Substance Use Disorders (SUD’s). Application of machine learning algorithms to such data could find diagnostic utility as biomarkers both to define the presence of the disorder and to quantitate its severity and find myriad applications in a developmental pipeline towards therapeutics and cure. Recent epigenomic studies have uncovered a wealth of clinically important data relating to synapse-nucleus signalling, memory storage, lineage-fate determination and cellular control and are contributing greatly to our understanding of all SUD’s. Epigenetics interacts extensively with glycobiology. Glycans decorate DNA, RNA and many circulating critical proteins particularly immunoglobulins. Glycosylation is emerging as a major information-laden post-translational protein modification with documented application for biomarker development. The integration of these two emerging cutting-edge technologies provides a powerful and fertile algorithmic-bioinformatic space for the development both of SUD biomarkers and novel cutting edge therapeutics. Hypotheses: These lines of evidence provide fertile ground for hypotheses relating to both diagnosis and treatment. They suggest that biomarkers derived from epigenomics complemented by glycobiology may potentially provide a bedside diagnostic tool which could be developed into a clinically useful biomarker to gauge both the presence and the severity of SUD's. Moreover they suggest that modern information-based therapeutics acting on the epigenome, via RNA interference or by DNA antisense oligonucleotides may provide a novel 21st century therapeutic development pipeline towards the radical cure of addictive disorders. Such techniques could be focussed and potentiated by neurotrophic vectors or the application of interfering electric or magnetic fields deep in the medial temporal lobes of the brain.