Curated Optogenetic Publication Database

Abstract: The development of optical nano-bio interfaces is a fundamental step toward connecting biological networks and traditional electronic computing systems. Compared to conventional chemical and electrical nano-bio interfaces, the use of light as a mediator enables new type of interfaces with unprecedented spatial and temporal resolutions. In this paper, the state of the art and future research directions in optogenomic interfaces are discussed. Optogenomic interfaces are light-mediated nano-bio interfaces that allow the control of the genome, i.e., the genes and their interactions in the cell nucleus (and, thus, of all the cell functionalities) with (sub) cellular resolution and high temporal accuracy. Given its fundamental role in the process of cell development, the study is focused on the interactions with the fibroblast growth factor receptor 1 (FGFR1) gene and the integrative nuclear FGFR1 signaling (INFS) module in stem cells and in neuronal cells, whose control opens the door to transformative applications, including reconstructive medicine and cancer therapy. Three stages of optogenomic interfaces are described, ranging from already experimentally validated interfaces activating broad cellular responses and expressing individual genes to more advanced interfaces able to regulate and correct DNA topology, chromatin structure, and cellular development.

Abstract: TDP-43 proteinopathy is a pathological hallmark of amyotrophic lateral sclerosis and frontotemporal dementia where cytoplasmic TDP-43 inclusions are observed within degenerating regions of patient postmortem tissue. The mechanism by which TDP-43 aggregates has remained elusive due to technological limitations, which prevent the analysis of specific TDP-43 interactions in live cells. We present an optogenetic approach to reliably induce TDP-43 proteinopathy under spatiotemporal control. We show that the formation of pathologically relevant inclusions is driven by aberrant interactions between low-complexity domains of TDP-43 that are antagonized by RNA binding. Although stress granules are hypothesized to be a conduit for seeding TDP-43 proteinopathy, we demonstrate pathological inclusions outside these RNA-rich structures. Furthermore, we show that aberrant phase transitions of cytoplasmic TDP-43 are neurotoxic and that treatment with oligonucleotides composed of TDP-43 target sequences prevent inclusions and rescue neurotoxicity. Collectively, these studies provide insight into the mechanisms that underlie TDP-43 proteinopathy and present a potential avenue for therapeutic intervention.