Computational analysis of the LRRK2 interactome

LRRK2 was identified in 2004 as the causative protein product of the Parkinson’s disease locus designated PARK8. In the decade since then, genetic studies have revealed at least 6 dominant mutations in LRRK2 linked to Parkinson’s disease, alongside one associated with cancer. It is now well established that coding changes in LRRK2 are one of the most common causes of Parkinson’s. Genome-wide association studies (GWAs) have, more recently, reported single nucleotide polymorphisms (SNPs) around the LRRK2 locus to be associated with risk of developing sporadic Parkinson’s disease and inflammatory bowel disorder. The functional research that has followed these genetic breakthroughs has generated an extensive literature regarding LRRK2 pathophysiology; however, there is still no consensus as to the biological function of LRRK2. To provide insight into the aspects of cell biology that are consistently related to LRRK2 activity, we analysed the plethora of candidate LRRK2 interactors available through the BioGRID and IntAct data repositories. We then performed GO terms enrichment for the LRRK2 interactome. We found that, in two different enrichment portals, the LRRK2 interactome was associated with terms referring to transport, cellular organization, vesicles and the cytoskeleton. We also verified that 21 of the LRRK2 interactors are genetically linked to risk for Parkin- son’s disease or inflammatory bowel disorder. The implications of these findings are discussed, with particular regard to potential novel areas of investigation.

Synapses in digital medium: computational investigations of neural basis of anticipation

Anticipation is an emerging concept that can provide a bridge between the deepest philosophical theories about the nature of life and cognition on one hand and the empirical biological sciences steeped in reductionist and Newtonian conception of causality. Three conceptions of anticipation have been emerging from the literature that may be operationalised in a way leading to a viable empirical programme. The discussion of the research into a novel dynamical concept of anticipating synchronisation lends credence to such a possibility and suggests further links between the three anticipation paradigms. A careful progress mindful to the deep philosophical concerns but also respecting empirical evidence will ultimately lead towards unifying theoretical and empirical biological sciences and may offer progress where reductionist science have been so far faltering.