Neural Pathway Bioinformatics
Cygnal is studying neural pathways in the context of human tumors and model systems. We examine both bulk tumor and single cell RNA sequencing to create novel neural signatures, including neural progenitors. We are using these signatures to probe human tumor samples and model systems to help us understand interactions between neurons and the tumor microenvironment.
Neural Functional Genomics
We use CRISPR screening technologies on a subset of the genome (the "neurome") to identify targets for drug development. Together with multiple in vitro and in vivo model systems, we uncover the role of exoneural genes in disease. In addition, our CRISPR screen data analysis identifies synthetic lethal paradigms of interest.
Neuroscience drug discovery efforts to date have generated hundreds of small and large molecules that we can use to interrogate neuronal protein function in the context of non-canonical disease systems. We use these tool molecules as part of our target ID, validation, and discovery efforts.
We have adapted co-culture systems to study neuron-cancer and neuron-immune cell interactions. We use these systems to interrogate changes in cell growth, migration, and cytokine profiles in target cells, directing us towards new pathways and targets for drug discovery.
Cygnal uses a combination of imaging methodologies including light sheet; confocal and electron microscopy combined with CLARITY; and immunofluorescence to characterize interactions between neurons and non-neuronal cells in multiple disease states. We define and quantitate these morphological features to enable screening.
Neural Cell Control
We've developed and adapted tools from neuroscience and applied them to neurons, both in vitro and in vivo, for the manipulation of neuronal function and the study of these functions on disease models. These powerful tools, which include chemogenetics and AAV delivery, allow for key target validation and proof-of-concept studies.