The FUNR Lab, lead by Flora Rutaganira uses choanoflagellates—the closest living single-celled relatives to animals—to study the origin of animal cell communication. We apply chemical, genetic, and cell biological tools to probe choanoflagellate cell-cell communication. We hope that our research has implications for understanding not only animal cell signaling, but also the origin of multicellularity in animals.
The overall goal of our laboratory is to uncover new regulatory mechanisms in signaling systems, to understand how these mechanisms are damaged in disease states and how to devise new new strategies to repair their function. Specific areas are highlighted below:
1. The Hedgehog and WNT pathways, two cell-cell communication systems that regulate the formation of most tissues during development. These same pathways play central roles in tissue stem-cell function and organ regeneration in adults. Defects in these systems are associated with degenerative conditions and cancer.
A central focus of our laboratory is to uncover new regulatory mechanisms in cell-cell communication system, understand how these mechanisms are damaged in disease states and devise strategies to repair their function. We are actively recruiting post-doctoral fellows to join projects in the following areas:
--Signaling pathways implicated in birth defects, cancer and regeneration.
--Regulation of signaling and development by primary cilia.
--Genetic and biochemical dissection of lipid pathways that regulate signaling, development and cancer.
Our laboratory studies the dynamics and organization of eukaryotic genomes. Every eukaryotic cell must compact its DNA into the nucleus while maintaining the accessibility of the DNA to the replication, repair, expression and segregation machinery. Eukaryotes accomplish this feat by assembling their genomes into chromatin and folding that chromatin into functional compartments.
We develop algorithms to predict and design the structures and energetics of RNAs and RNA/protein complexes. We test these ideas through community-wide blind trials; by enhancing NMR, crystallographic, and cryoelectron microscopy methods; and by designing new complexes. Upcoming projects involve directly visualizing how natural RNA machines work inside human cells and designing molecules that might enable RNA-based optogenetics, self-replication, and sequence-controlled synthesis of novel polymers.
Our lab seeks to understand the molecular basis of inherited Parkinson's Disease. Activating mutations in the LRRK2 kinase cause Parkinson's , and the major substrates of LRRK2 kinase are a subset of proteins called Rab GTPases. Together with our collaborators, we have discovered that phosphorylation of Rab proteins completely changes the partner proteins with which they interact and leads to a blockade in the formation of critical signaling structures called primary cilia. We are using biochemical, cell biological and genome-wide approaches to study the molecular cell biology of Parkins
The Yeh Lab studies the apicoplast, a unique plastid organelle in Plasmodium falciparum parasites that cause malaria. We are particularly focused on unbiased chemical and genetic screens to discover new cell biology and therapeutic targets for this important global health disease. Our work highlights the untapped opportunities in exploring divergent biology in non-model organisms, a theme we plan to expand in the lab by studying ocean algae (malaria's cousins!) and their role in the global ecosystem.
Our lab uses cellular, biochemical, and genetic approaches to understand the mechanism by which developmental signaling pathways, such as the WNT and Hedgehog pathways, function and how they are damaged in disease states. We use a broad range of approaches in our work: genome-wide CRISPR screens, proteomics, imaging, and both protein and lipid biochemistry.
Statistical algorithms for genomics, RNA biology, splicing, cancer genomics, spatial transcriptomics
