Communication and networking play a key role in the development and functioning of living organisms. The physical DNA interactions within the genome, or network of genes, determine gene activities and thereby the development and function of cells, similarly as the software determines the operation of the hardware in a computer. Therefore, being able to program genomic interactions and thereby the development of communicating neuronal networks is at the basis of transformative applications. In this direction, optogenomics, or the control of the genome function through light, is proposed. Optogenomics offers an unprecedented means to control organ and specifically brain development and functions, or even new corrective treatments of cancer and other diseases. Such control will be enabled through development of novel directional light emitting nano-devices. The goal of this inter-disciplinary project is to study information processing and learning (and, thus, ultimately memory) in neuronal networks orchestrated by the light manipulation of the genome. For this, new photonic and electronic tools will be developed to program the genome in neurons and to study both the resulting changes in the structure and activity in networks of living neurons. This project will provide inter-disciplinary training opportunities for graduate and undergraduate students, who will become versed in both nanophotonics and nanoelectronics as well as neuronal cell studies.
Beyond optogenetic platforms, which are aimed at the use of light to control cell-cell interactions, optogenomic systems allow the control of DNA interactions in the genome and, thus, the programming of the cell development and function. In this project, new optogenomic tools will be developed to control the development and information processing and learning in neuronal networks. In the proposed system, neural stem cells will be transfected with optimized optogenomic constructs that combine light-activated algae proteins and mammalian genome regulators. As the input to the system, the constructs will be activated globally across the cell culture through LED-based homogeneous illumination. The light-induced changes in the genome 3D structure and function will be analyzed using Chromatin Conformation Capture HiC/HiChIP, Atomic Force Microscopy, and RNAseq with the NextGene global genome sequencing. The output of the system will be the opto-electrophysiological analysis of signal processing in optogenomically constructed neuronal networks, with innovative transparent flexile beamforming nanophotonic devices combined with flexible high-density microelectrode arrays, using metrics like Spike-Timing-Dependent Plasticity, Hebbian learning and network science. An integrated Genome-Neuronal Function Model will be developed for the first time by correlating genomic topological networks to the functional gene networks and ultimately to the properties of the resultant neuronal network as they form in 3D model of the human brain – cerebral organoids.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
