Diversity in Notch ligand-receptor signaling interactions.

The Notch signaling pathway uses families of ligands and receptors to transmit signals to nearby cells. These components are expressed in diverse combinations in different cell types, interact in a many-to-many fashion, both within the same cell (in cis) and between cells (in trans), and their interactions are modulated by Fringe glycosyltransferases. A fundamental question is how the strength of Notch signaling depends on which pathway components are expressed, at what levels, and in which cells.

A synthetic protein-level neural network in mammalian cells.

Artificial neural networks provide a powerful paradigm for nonbiological information processing. To understand whether similar principles could enable computation within living cells, we combined de novo-designed protein heterodimers and engineered viral proteases to implement a synthetic protein circuit that performs winner-take-all neural network classification. This "perceptein" circuit combines weighted input summation through reversible binding interactions with self-activation and mutual inhibition through irreversible proteolytic cleavage.

The lives of cells, recorded.

A paradigm for biology is emerging in which cells can be genetically programmed to write their histories into their own genomes. These records can subsequently be read, and the cellular histories reconstructed, which for each cell could include a record of its lineage relationships, extrinsic influences, internal states and physical locations, over time. DNA recording has the potential to transform the way that we study developmental and disease processes.

Simultaneous Protein and RNA Analysis in Single Extracellular Vesicles, Including Viruses.

The individual detection of human immunodeficiency virus (HIV) virions and resolution from extracellular vesicles (EVs) during analysis is a difficult challenge. Infectious enveloped virions and nonviral EVs are released simultaneously by HIV-infected host cells, in addition to hybrid viral EVs containing combinations of HIV and host components but lacking replicative ability. Complicating the issue, EVs and enveloped virions are both delimited by a lipid bilayer and share similar size and density.