@timcyuu

phd student @mcbseattle in the @jbloom_lab wondering how viruses evolve

 Seattle, WA
Joined July 2019
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  • Following263
  • Followers124
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In new study led by @timcyuu, we measure how mutations to H3 flu HA affect cell entry, stability & antibody escape We find pleiotropic effects of mutations on these phenotypes shape evolution: epistasis alleviates cell-entry but not stability constraints biorxiv.org/content/10.1101/…

Pleiotropic mutational effects on function and stability constrain the antigenic evolution of...

The evolution of human influenza virus hemagglutinin (HA) involves simultaneous selection to acquire antigenic mutations that escape population immunity while preserving protein function and stabil...

biorxiv.org
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In study led by @CKikawa & Andrea Loes, we use new assay to measure ~10,000 neutralization titers to recent influenza strains & show titers correlate w evolutionary success of viral strains Similar data could help forecast evolution for vaccine selection biorxiv.org/content/10.1101/…

High-throughput neutralization measurements correlate strongly with evolutionary success of human...

Human influenza viruses rapidly acquire mutations in their hemagglutinin (HA) protein that erode neutralization by antibodies from prior exposures. Here, we use a sequencing-based assay to measure...

biorxiv.org
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Congrats @gracecbower!
Grace Bower@gracecbower27 May 2024
Beyond proud of the work that went into our latest story! A big shoutout to @evgenykvon for the incredible guidance.
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How do enhancers work over distances that sometimes exceed megabases? Excited to share our work led by @gracecbower where we uncover a unique sequence signature globally associated with long-range enhancer-promoter interactions in developing limb buds: biorxiv.org/content/10.1101/… 1/
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In new study led by @bdadonaite, we measure how all mutations to H5 influenza HA affect four molecular phenotypes relevant to pandemic risk: biorxiv.org/content/10.1101/… Results can inform surveillance of ongoing evolution of H5N1.
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In new study led by @bblarsen1 in collab w @veeslerlab @VUMC_Vaccines we map functional & antigenic landscape of Nipah virus receptor binding protein (RBP) biorxiv.org/content/10.1101/… Results elucidate constraints on RBP function & provide insight re protein’s evolutionary potential

Functional and antigenic landscape of the Nipah virus receptor binding protein

Nipah virus recurrently spills over to humans, causing fatal infections. The viral receptor-binding protein (RBP or G) attaches to host receptors and is a major target of neutralizing antibodies....

biorxiv.org
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In new study led by Andrea Loes, we develop sequencing-based neutralization assay that measures replicate curves for hundreds of virus-serum pairs per 96-well plate (see image below) biorxiv.org/content/10.1101/… We apply assay to characterize response to repeat influenza vaccination
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In new study led by Caleb Carr & @khdcrawford, we measure how all mutation to Lassa virus glycoprotein complex (GPC) affect cell entry & antibody escape Results show how prospective assessment of effects of mutations can inform design of countermeasures biorxiv.org/content/10.1101/…

Deep mutational scanning reveals functional constraints and antigenic variability of Lassa virus...

Lassa virus is estimated to cause thousands of human deaths per year, primarily due to spillovers from its natural host, Mastomys rodents. Efforts to create vaccines and antibody therapeutics must...

biorxiv.org
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In new study led by Frances Welsh, we map how mutations to influenza affect neutralization by antibodies from humans of various ages We find differences in mutation effects among age groups Virus has evolved especially to escape antibodies of teenagers biorxiv.org/content/10.1101/…

Age-dependent heterogeneity in the antigenic effects of mutations to influenza hemagglutinin

Human influenza virus evolves to escape neutralization by polyclonal antibodies. However, we have a limited understanding of how the antigenic effects of viral mutations vary across the human...

biorxiv.org
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Thrilled to announce my first first-author paper of grad school has been accepted at @eLife! Shoutout to @turcotteea, my 2 awesome labs, and my two amazing advisors Michael Emerman and @psmitchej. Check it out here: elifesciences.org/articles/8…

A human-specific motif facilitates CARD8 inflammasome activation after HIV-1 infection

HIV-1 infection activates the human CARD8 inflammasome via innate immune recognition of HIV-1 viral protease activity.

elifesciences.org
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In a new study led by @CaelanRadford in collaboration with @FKlein_lab, we use an improved deep mutational scanning system to map the neutralizing specificities of broad human polyclonal serum antibodies from individuals living with HIV. biorxiv.org/content/10.1101/…

Mapping the neutralizing specificity of human anti-HIV serum by deep mutational scanning

Understanding the specificities of human serum antibodies that broadly neutralize HIV can inform prevention and treatment strategies. Here we describe a deep mutational scanning system that can...

biorxiv.org
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Final version of our paper on deep mutational scanning system to measure antigenic and functional effects of mutations to full SARS-CoV-2 spike: cell.com/cell/fulltext/S0092… System uses non-replicative lentiviral pseudotypes to safely map effects of thousands of spike mutations.

A pseudovirus system enables deep mutational scanning of the full SARS-CoV-2 spike

A high-throughput deep mutational scanning platform that uses non-replicative pseudotyped lentiviruses is able to directly quantify how SARS-CoV-2 spike mutations affect antibody neutralization and...

cell.com
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In work led by @bdadonaite @khdcrawford @CaelanRadford, we develop pseudovirus system to deep mutational scan full #SARSCoV2 spike: biorxiv.org/content/10.1101/… TLDR: can now safely measure how all mutations to viral entry proteins affect antibody neutralization. 🧵 below (1/n)

A pseudovirus system enables deep mutational scanning of the full SARS-CoV-2 spike

A major challenge in understanding SARS-CoV-2 evolution is interpreting the antigenic and functional effects of emerging mutations in the viral spike protein. Here we describe a new deep mutational...

biorxiv.org
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First manuscript of grad school now live on bioRxiv! Check it out ;) So excited and thankful to @psmitchej and @memerman for their amazing guidance.
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Our newest study is up, where we report deep mutational scanning data in the Omicron BA.1 and BA.2 receptor-binding domains biorxiv.org/content/10.1101/…

Deep mutational scans for ACE2 binding, RBD expression, and antibody escape in the SARS-CoV-2...

SARS-CoV-2 continues to acquire mutations in the spike receptor-binding domain (RBD) that impact ACE2 receptor binding, folding stability, and antibody recognition. Deep mutational scanning prospec...

biorxiv.org
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Excited to share our preprint on modeling viral escape from polyclonal antibodies. Check out the thread by @jbloom_lab for more details!
Bloom Lab
@jbloom_lab18 Sep 2022
In new work, we formulate a biophysical model of viral escape from polyclonal antibodies, & develop software to apply model to deep mutational scanning data to understand antigenic effects of combinations of mutations: biorxiv.org/content/10.1101/… I explain in 🧵 below.

A biophysical model of viral escape from polyclonal antibodies

A challenge in studying viral immune escape is determining how mutations combine to escape polyclonal antibodies, which can potentially target multiple distinct viral epitopes. Here we introduce a...

biorxiv.org
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In new study, we examine how target cell ACE2 expression affects #SARSCoV2 neutralization biorxiv.org/content/10.1101/… We find high-ACE2 cells emphasize role of RBD antibodies in serum & lower ACE2 cells reveal more neutralization by antibodies to other regions of spike. 🧵 below:
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In new study led by @dbacsik, we show single influenza-infected cells produce wildly different numbers of viral progeny: biorxiv.org/content/10.1101/… Surprisingly, cells that transcribe the most viral mRNA are NOT ones that produce the most progeny virions. Explanatory 🧵 below

Influenza virus transcription and progeny production are poorly correlated in single cells

The ultimate success of a viral infection at the cellular level is determined by the number of progeny virions produced. However, most single-cell studies of infection quantify the expression of...

biorxiv.org
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🥳 Excited to share that the Starr Lab is coming to the University of Utah @UofUBiochem! Check out the lab website to see where we’re headed in our studies of protein evolution in viruses and immunity starr.biochem.utah.edu

Starr Lab

starr.biochem.utah.edu
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We have new data on the effects of all RBD mutations to Omicron BA.1 and BA.2 on ACE2 affinity & RBD expression. These data, which are from experiments and analyses by @tylernstarr @AllieGreaney & Will Hannon are available here for viewing and download: jbloomlab.github.io/SARS-CoV…

SARS-CoV-2 RBD deep mutational scanning in variants of concern

Shifting mutational constraints in the SARS-CoV-2 receptor-binding domain during viral evolution.

jbloomlab.github.io
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