The ARRIBERE LAb

INTRODUCTION

We are a lab studying RNA and protein metabolism at UC Santa Cruz. We are especially interested in the oft-overlooked processes of regulated mRNA decay, and in proteins that don't quite make it to maturity. We love genetics coupled with novel technologies and quantitative reasoning. We are housed in the MCD Biology Department, and we are proud members of the UCSC RNA Center and the Genomics Institute.

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RESEARCH

Overview

Gene expression, the process by which our cells decode genomic information, is subject to gene-specific variations leading to drastically different outcomes in protein and mRNA expression. At one extreme are mRNA quality control pathways that detect and remove mRNAs with certain mutations, such as translation elongation stalls, a lack of stop codons, or an early stop codon. These pathways are conserved and highly relevant to human disease: eleven percent of human inherited disease-causing alleles introduce a premature stop codon. The overarching goal of the Arribere Lab is to discover–in molecular detail–the mechanisms, substrates, and pathways that various mRNAs take in the cell.

Quality Control of Gene Expression

Mistakes occur during the replication and decoding of the genome. Cells contend with and mitigate the products of such errors through quality control. Quality control can fail in two ways: (1) cells can fail to identify or remove abnormal proteins or (2) cells can inappropriately remove otherwise functional gene products. Both types of failures can cause genetic disease, highlighting the importance of quality control in gene expression. Cells can also exploit quality control for the regulation of ‘normal’ genes. We aim to uncover how these surveillance mechanisms work. We hope to pioneer methodologies and models useful for the future study of quality control in gene expression by both scientists and medical researchers. A long-term goal of the lab is to determine how these processes could be enhanced or abrogated to the benefit of human health.

Old & New Technologies

We use a powerful combination of established and novel techniques. Classical genetics are a mainstay of the lab: C. elegans genetic analyses, phenotypic reporters, and forward genetic screens form the backbone of many projects, pointing us to molecular machinery involved. We also enjoy interrogating mRNA metabolism with novel technologies (nanopore sequencing, Artificial Intelligence-based structure prediction, cryo-Electron Microscopy) to attain new vantage points from which to understand mRNA and protein metabolism.

PEOPLE

The Arribere Lab tie-dying t-shirts at an event hosted by the o-STEM club, circa Sept 2024

Associate Professor Joshua Arribere

Josh received dual Bachelors in Molecular & Cell Biology and Applied Mathematics from UC Berkeley. While an undergrad, he studied alternative splicing in zebrafish development with Dr. John Conboy (LBNL) and Prof. Sharon Amacher. He completed his PhD under Prof. Wendy Gilbert at MIT where he learned to love computational biology, mRNAs' 5'ends, and ribosomes. As a postdoc with Prof. Andrew Fire at Stanford he learned the ways of the worm (C. elegans), the power of genetics, and the beauty of well-designed experiments.