Biology subjects

Edilbi, D.

Publications and source records attributed to Edilbi, D..

3 recordsLinked to original sources

bioRxiv2025

A pipeline for screening condition-specific enzymes uncovers a function for the alcohol dehydrogenase Bdh2

Cells possess intricate metabolic networks comprised of hundreds of enzymes. Despite extensive research, many of these enzymes remain uncharacterized. Identifying such enzymes is crucial for advancing our understanding of metabolism. However, multiple enzymes are not expressed in standard conditions, making them challenging to study. To overcome this challenge, we created a pipeline for characterizing the expression of condition-specific enzymes in yeast. We assembled a collection of 110 yeast strains, each containing an uncharacterized putative enzyme fused to a fluorophore under the regulation of their own promotor. By subjecting them to 43 diverse growth or stress environments, we identified the biologically relevant conditions for the expression of 19 proteins. We focused on one such putative alcohol dehydrogenase, Bdh2, and functionally characterized it. More broadly, our discovery pipeline lays the foundation for uncovering new condition-specific enzymes. This has implications in cell biology and biotechnology and should expand our understanding of metabolism.

cell biology↗

bioRxiv2024

A proteome-wide yeast degron collection for the dynamic study of protein function.

Genome-wide collections of yeast strains, known as libraries, revolutionized the way systematic studies are carried out. Specifically, libraries that involve a cellular perturbation, such as the deletion collection, have facilitated key biological discoveries. However, short-term rewiring and long-term accumulation of suppressor mutations often obscure the functional consequences of such perturbations. We present the AID library which supplies "on demand" protein depletion to overcome these limitations. Here, each protein is tagged with a Green Fluorescent Protein (GFP) and an Auxin inducible degron (AID), enabling rapid protein depletion that can be quantified systematically using the GFP element. We characterized the degradation response of all strains and demonstrated its utility by revisiting seminal yeast screens for genes involved in cell cycle progression as well as mitochondrial distribution and morphology. In addition to recapitulating known phenotypes, we also uncovered proteins with previously unrecognized roles in these central processes. Hence, our tool expands our knowledge of cellular biology and physiology by enabling access to phenotypes that are central to cellular physiology and therefore rapidly equilibrated.

cell biology↗

bioRxiv2023

TREM2-dependent senescent microglia conserved in aging and Alzheimer's disease

Dementia in general, and Alzheimers disease (AD) in particular, are age-related diseases1,2. AD is associated with multiple causative factors3,4, among which local brain inflammation plays a significant role5. Microglia, the brain-resident immune cells6,7, are activated along the disease course7. Yet, their contribution to the disease progression is still controversial. Here, using high-throughput mass cytometry for microglial immuno-phenotyping, we identified accumulation of senescent microglia in several pathologies associated with cognitive decline. These senescent microglia have a unique profile conserved across the multiple conditions investigated, including aging, mouse models of amyloidosis, and tauopathy. Moreover, we found that the expression of markers of senescence correlates with levels of TREM2, whose polymorphism was identified by GWAS as an AD risk factor8,9. A TREM2-null AD mouse model showed lower levels of senescent microglia, relative to TREM2-intact AD mice. Senolysis using the drug ABT-73710,11 in an AD mouse model reduced the abundance of TREM2-senescent microglia without affecting levels of TREM2-dependent activated microglia, ameliorated cognitive deficits, and reduced brain inflammation. These results reveal the unexpected contribution of TREM2 to accumulation of senescent microglia in AD pathology, an effect that must be considered when targeting TREM2 as a therapeutic approach.

neuroscience↗