Aviner Group: Ribosomes and Human Disease

Our Research

Ribosomes are ancient molecular machines essential for all life. We explore how and why they are disrupted during viral infection and neurodegeneration.

How do ribosomes change in disease? And how can such changes guide us towards therapeutics?

Ribosomes exist as dynamic heterogenous subpopulations that preferentially synthesize different sets of proteins. Such heterogenicity is driven by interaction with non-ribosomal proteins that bind RNA or nascent chain motifs and form remarkably intricate networks that govern the fate of the proteome.

Using a combination of molecular biology, transcriptomics, and proteomics, we monitor how these networks are remodeled during acute viral infection and chronic neurodegeneration. We harness this knowledge for rational design of therapeutic interventions.


Rethinking antiviral drug discovery

Traditionally, antiviral drugs target viral enzymes, often leading to rapid acquisition of resistance. An alternative approach is to target host components that are both essential for the virus and dispensable for short-term host function. Our work aims to discover and characterize host-targeted strategies for broad-spectrum, low-resistance antiviral.

Tools to explore ribosome function

Rapid developments in high-throughput technologies have revolutionized our understanding of protein synthesis. Our work expands the available toolkit for monitoring ribosome function by developing molecular and omic-level assays to monitor translation and nascent chain dynamics. We are currently adapting these to study translation errors and organism-specific differences in viral infection.

Ribosome dysfunction in neurodegenerative disease

Many types of human disease disrupt ribosome function. By analyzing ribosomes from mouse models of Huntington’s Disease (HD), we found that neurotoxicity is associated with depletion of a key regulator of ribosome function. Building on this new understanding of a key regulator of disease etiology, we seek to determine whether manipulating the translation machinery can delay cell death in HD.