About

Gloria Brar is an Associate Professor of Molecular and Cell Biology and is part of the Designated Emphasis Faculty at the Center for Computational Biology. She is involved in research and academic activities related to computational biology, with a focus on integrating computational methods with biological research. Her role includes mentoring students and contributing to the academic community at UC Berkeley, particularly within the Department of Molecular and Cell Biology. She is contactable via gabrar@berkeley.edu and is associated with the DE Student Giselle Uribe and Alejandro Collins.

Research topics

• Computer Science
• Biology
• Genetics
• Artificial Intelligence
• Computational biology
• Chemistry
• Engineering ethics
• Engineering
• Environmental ethics
• Cell biology
• Epistemology
• Telecommunications

Selected publications

• Glutamine codon-driven translational readthrough reveals context-dependent stop codon decoding fidelity

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-05-11

  articleOpen access

  ABSTRACT Deviations from the canonical genetic code include reassignment of UAA/UAG stop codons to glutamine in divergent eukaryotes, and tRNA Gln has been shown to mediate near-cognate stop codon readthrough in canonical-code organisms. However, the sequence determinants and mechanistic basis of this decoding event remain poorly understood. Using ribosome profiling, quantitative immunoblotting, and mass spectrometry in Saccharomyces cerevisiae , we demonstrate that premature stop codon readthrough efficiency is governed by both local glutamine codon context and the global glutamine codon content of the mRNA. A QXQ motif flanking the stop codon promotes baseline readthrough, which is amplified in proportion to total transcript glutamine codon abundance. Mass spectrometry confirms that glutamine is specifically inserted at the premature stop, with no flanking miscoding, implicating tRNA Gln competition with the release factor as the mechanistic basis of readthrough. Consistent with this model, yeast proteins terminating in short C-terminal glutamine repeats are evolutionarily enriched for strong stop codon contexts, suggesting selective pressure to reinforce termination fidelity at readthrough-prone loci.

  PublisherOA PDFDOI

• SPRINT-MS: A high-throughput platform for identifying protein-protein interactions using pooled IP-MS and sparse signal recovery

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-11-21 · 1 citations

  preprintOpen access

  Abstract We present SPRINT-MS (SParse Reconstruction of INTeractions by Mass Spectrometry), an integrated experimental and computational platform to accelerate the discovery of protein-protein interactions (PPIs). PPIs, which govern critical cellular and physiological processes such as development and disease, form extensive networks that vary across time, conditions, and cell types, creating a complex, high-dimensionality problem. Thus, there is a pressing need for universally applicable tools capable of mapping and quantifying PPI networks and their context-dependent dynamics with high efficiency. SPRINT-MS combines an innovative antibody (or lysate) pooling scheme, immunopurification-mass spectrometry (IP-MS), and a novel sparse signal reconstruction algorithm to enable pooled PPI capture experiments. This approach increases throughput by an order of magnitude, while reducing sample input requirements. We demonstrate that SPRINT-MS, applied to 30 bait proteins of interest via either antibody or lysate pooling, is comparable to standard individual IP-MS experiments in the identification of PPIs and recapitulation of known interactions.

  PublisherDOI

• Tom70-mediated mitochondria–nuclear envelope contacts regulate nuclear pore complex inheritance during gametogenesis

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-11-21

  preprintOpen access

  Abstract Gametogenesis rejuvenates the cellular lineage and excludes senescence-associated factors from gametes. In Saccharomyces cerevisiae , this involves sequestration of nuclear constituents into the Gametogenesis-Uninherited Nuclear Compartment (GUNC), which is excluded from gametes. Here we identify the conserved mitochondrial import receptor Tom70 as a key regulator of GUNC-mediated exclusion. Loss of TOM70 disrupts the sequestration of nuclear pore complexes, but not senescence-associated aggregates and nucleolar components, into the GUNC. Tom70’s role appears independent of its canonical function in mitochondrial import and instead reflects a meiosis-specific requirement for mitochondria-nuclear envelope tethering. During meiosis II, Tom70 concentrates around the GUNC, where it recruits the nuclear envelope tethering protein Cnm1. Loss of CNM1 partially phenocopies tom70Δ , consistent with parallel tethering interactions. These findings uncover a previously unrecognized organelle contact-dependent pathway that remodels the nuclear envelope to support selective nuclear inheritance. More broadly, they highlight how organelle contacts integrate with nuclear quality control to safeguard gamete integrity.

  PublisherDOI

• A role for selective autophagy of the ER in gametogenic rejuvenation revealed by microfluidics-based lifespan profiling

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-10-08 · 2 citations

  preprintOpen accessSenior author

  Abstract During mitotic growth, Saccharomyces cerevisiae cells age by dividing asymmetrically producing young daughter cells while retaining age-associated damage in the mother cell, which will eventually become senescent. Gametogenesis naturally and fully resets precursor cell lifespan, even for replicatively aged cells. However, the mechanisms responsible for gametogenic rejuvenation remain elusive. This is, in part, due to the existing methods to quantify replicative lifespan resetting in this context, which are limited to low-throughput and labor-intensive approaches. Here, we introduce a high-throughput microfluidic-based assay that allows systematic characterization of factors required for gametogenic rejuvenation in S. cerevisiae. With this technique, we show that we can sensitively measure a wide range of gamete replicative lifespans that are consistent with known short and long-lived mutants. Excitingly, using this technique, we report Atg39 and Atg40, receptors involved in selective autophagy of the ER, as the first identified molecular determinants of gametogenic rejuvenation. We anticipate that this novel technique will enable systematic identification of additional molecular factors that drive gametogenic rejuvenation.

  PublisherOA PDFDOI

• Proteasome activator Blm10 maintains cellular proteostatic balance and gamete quality in budding yeast

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-12-11

  articleOpen accessSenior authorCorresponding

  The proteasome is the central macromolecular complex that is responsible for regulated protein degradation in eukaryotic cells. Its best characterized substrates are ubiquitinated proteins that are targeted to the 26S proteasome complex, consisting of a 19S regulatory particle (RP) capping the barrel-shaped 20S core peptidase (CP). The CP can interact with other caps that modulate its function, including Blm10/PA200, a large monomeric protein whose biological function is not well understood. Blm10 is highly upregulated during gametogenesis in budding yeast, suggestive of a natural stage-specific modulation of proteasome composition. Here, we investigate the function Blm10 during yeast gametogenesis, identifying it as a weak activator of the proteasome that can displace the 19S RP from the CP. Due to this competition for the CP, overexpression of Blm10 can lead to attenuation of ubiquitin-dependent degradation and consequent proteostatic defects. Cells lacking Blm10 also display markers of proteostatic stress, including Hsp104 foci and heat sensitivity, suggesting that Blm10 safeguards normal proteostatic balance. We find that Blm10 is important for maintaining gamete fitness and ensuring normal rejuvenation of aged cells following gametogenesis. Overall, our data suggest a role for Blm10-proteasomes in maintaining gamete proteostasis through fine-tuning of proteasome activity and prevention of protein aggregation.

  PublisherOA PDFDOI

• UPR deficiency leads to poor growth, aneuploidy, and a trade-off between ER and general proteostasis in yeast

  Genes & Development · 2025-08-22 · 1 citations

  articleOpen accessSenior author

  The unfolded protein response (UPR) was discovered in budding yeast as a mechanism that allows cells to adapt to endoplasmic reticulum (ER) stressors. Although the UPR is not thought to be necessary for cellular fitness of wild-type cells in the absence of stress, we found that UPR deficiency led to poor growth in cycling mitotic yeast cells. This led to pervasive adaptive aneuploidy of specific chromosomes that was seen in divergent strain backgrounds, indicating an important basal role for this pathway that was missed by studies of the most common laboratory-derived strains. Aneuploid UPR-deficient cells grew better than euploid UPR-deficient cells but exhibited heightened general proteostatic stress, a hallmark of aneuploidy in wild-type cells. Modulation of key genes involved in ER proteostasis that were encoded on aneuploid chromosomes could phenocopy the effects of aneuploidy, indicating that the reason UPR-deficient cells become aneuploid is to counteract protein folding stress in the ER. Proteomic analyses indicate that expression of a small subset of stress-induced UPR targets is supported by basal UPR activity, including the chaperone Kar2/BiP. Together, our results reveal an unexpected role for the UPR in baseline ER folding that is important enough to safeguard cellular fitness that cells tolerate the substantial proteostatic costs that result from aneuploidy to counteract its loss.

  PublisherOA PDFDOI

• Analyses of translation factors Dbp1 and Ded1 reveal the cellular response to heat stress to be separable from stress granule formation

  Cell Reports · 2024-12-01 · 2 citations

  articleOpen accessSenior author

  Ded1 and Dbp1 are paralogous conserved DEAD-box ATPases involved in translation initiation in yeast. In long-term starvation states, Dbp1 expression increases and Ded1 decreases, whereas in cycling mitotic cells, Dbp1 is absent. Inserting DBP1 in place of DED1 cannot replace Ded1 function in supporting mitotic translation, partly due to inefficient translation of the DBP1 coding region. Global translation measurements, activity of mRNA-tethered proteins, and growth assays show that-even at matched protein levels-Ded1 is better than Dbp1 at activating translation, especially for mRNAs with structured 5' leaders. Heat-stressed cells normally downregulate translation of structured housekeeping transcripts and halt growth, but neither occurs in Dbp1-expressing cells. This failure to halt growth in response to heat is not based on deficient stress granule formation or failure to reduce bulk translation. Rather, it depends on heat-triggered loss of Ded1 function mediated by an 11-amino-acid interval within its intrinsically disordered C terminus.

  PublisherDOI

• Dbp1 is a low performance paralog of RNA helicase Ded1 that drives impaired translation and heat stress response

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-01-14 · 3 citations

  preprintOpen accessSenior authorCorresponding

  Abstract Ded1 and Dbp1 are paralogous conserved RNA helicases that enable translation initiation in yeast. Ded1 has been heavily studied but the role of Dbp1 is poorly understood. We find that the expression of these two helicases is controlled in an inverse and condition-specific manner. In meiosis and other long-term starvation states, Dbp1 expression is upregulated and Ded1 is downregulated, whereas in mitotic cells, Dbp1 expression is extremely low. Inserting the DBP1 ORF in place of the DED1 ORF cannot replace the function of Ded1 in supporting translation, partly due to inefficient mitotic translation of the DBP1 mRNA, dependent on features of its ORF sequence but independent of codon optimality. Global measurements of translation rates and 5’ leader translation, activity of mRNA-tethered helicases, ribosome association, and low temperature growth assays show that—even at matched protein levels—Ded1 is more effective than Dbp1 at activating translation, especially for mRNAs with structured 5’ leaders. Ded1 supports halting of translation and cell growth in response to heat stress, but Dbp1 lacks this function, as well. These functional differences in the ability to efficiently mediate translation activation and braking can be ascribed to the divergent, disordered N- and C-terminal regions of these two helicases. Altogether, our data show that Dbp1 is a “low performance” version of Ded1 that cells employ in place of Ded1 under long-term conditions of nutrient deficiency.

  PublisherOA PDFDOI

• Truncated protein isoforms generate diversity of protein localization and function in yeast

  Cell Systems · 2024-04-01 · 17 citations

  articleOpen accessSenior authorCorresponding
  PublisherOA PDFDOI

• UPR deficiency in budding yeast reveals a trade-off between ER folding capacity and maintenance of euploidy

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-11-24 · 1 citations

  preprintOpen accessSenior authorCorresponding

  The Unfolded Protein Response (UPR) was discovered in budding yeast as a mechanism that allows cells to adapt to ER stress. While the Ire1 branch of this pathway is highly conserved, it is not thought to be important for cellular homeostasis in the absence of stress. Surprisingly, we found that removal of UPR activity led to pervasive aneuploidy in budding yeast cells, suggesting selective pressure resulting from UPR-deficiency. Aneuploid UPR-deficient cells grew better than euploid cells, but exhibited heightened general proteostatic stress, a hallmark of aneuploidy in wild-type cells. Modulation of key genes involved in ER proteostasis that were encoded on aneuploid chromosomes, could phenocopy the effects of aneuploidy, indicating that the reason cells require UPR activity to maintain euploidy is to counteract protein folding stress in the ER. In support of this model, aneuploidy in UPR-deficient cells can be prevented by expression of a UPR-independent general ER chaperone. Overall, our results indicate an unexpected role for the UPR in basal cell growth that is sufficiently important for cells to accept the costly trade-off of aneuploidy in the absence of UPR activity.

  PublisherOA PDFDOI

Recent grants

• Illuminating the gene regulatory strategies underlying yeast meiosis and beyond

  NIH · $3.1M · 2020–2029

• Dissecting the roles of pervasive short ORFs in meiosis

  NIH · $2.4M · 2015–2020

• Defining the programmed proteome rejuvenation underlying gametogenesis

  NIH · $2.9M · 2021–2027

Frequent coauthors

• Jonathan S. Weissman

  Whitehead Institute for Biomedical Research

  100 shared

• Nicholas T. Ingolia

  QB3

  52 shared

• Angelika Amon

  Massachusetts Institute of Technology

  39 shared

• Noam Stern‐Ginossar

  Weizmann Institute of Science

  25 shared

• Nicolas Thierry‐Mieg

  24 shared

• Aviv Regev

  Broad Institute

  22 shared

• Ina Hollerer

  University of California, Berkeley

  20 shared

• Jennifer A. Doudna

  University of California, Berkeley

  20 shared