Steven Boeynaems

UT Southwestern researcher receives NIH Director’s New Innovator Award David Sanders, Ph.D., Assistant Professor in the Center for Alzheimer’s and Neurodegenerative Diseases and Molecular Biology at UT Southwestern Medical Center, has been awarded $2.4 million over five ...

Humbled to announce that we received a New Innovator award. I thank the NIH’s civil servants for their hard work during a stressful funding cycle. I thank the leadership (and chair, Marc Diamond) at UTSW for betting on my lab’s high risk, high reward research. www.utsouthwestern.edu/newsroom/art...

Dr. Graham Erwin @grahamerwin.bsky.social receives NIH New Innovator Award! www.bcm.edu/news/dr-grah... @bcmhouston.bsky.social @bcmgenetics.bsky.social #BCMCancerCenter

Sperm sequencing reveals extensive positive selection in the male germline - Nature A combination of whole-genome NanoSeq with deep whole-exome and targeted NanoSeq is used to accurately characterize mutation rates and genes under positive selection in sperm cells.

Now published! Our paper on:
(1) Accurate sequencing of sperm at scale
(2) Positive selection of spermatogenesis driver mutations across the exome
(3) Offspring disease risks from male reproductive aging
[1/n]
www.nature.com/articles/s41...

Lysine deserts prevent adventitious ubiquitylation of ubiquitin-proteasome components - Cellular and Molecular Life Sciences In terms of its relative frequency, lysine is a common amino acid in the human proteome. However, by bioinformatics we find hundreds of proteins that contain long and evolutionarily conserved stretches completely devoid of lysine residues. These so-called lysine deserts show a high prevalence in intrinsically disordered proteins with known or predicted functions within the ubiquitin-proteasome system (UPS), including many E3 ubiquitin-protein ligases and UBL domain proteasome substrate shuttles, such as BAG6, RAD23A, UBQLN1 and UBQLN2. We show that introduction of lysine residues into the deserts leads to a striking increase in ubiquitylation of some of these proteins. In case of BAG6, we show that ubiquitylation is catalyzed by the E3 RNF126, while RAD23A is ubiquitylated by E6AP. Despite the elevated ubiquitylation, mutant RAD23A appears stable, but displays a partial loss of function phenotype in fission yeast. In case of UBQLN1 and BAG6, introducing lysine leads to a reduced abundance due to proteasomal degradation of the proteins. For UBQLN1 we show that arginine residues within the lysine depleted region are critical for its ability to form cytosolic speckles/inclusions. We propose that selective pressure to avoid lysine residues may be a common evolutionary mechanism to prevent unwarranted ubiquitylation and/or perhaps other lysine post-translational modifications. This may be particularly relevant for UPS components as they closely and frequently encounter the ubiquitylation machinery and are thus more susceptible to nonspecific ubiquitylation.

For our previous work on lysine deserts see

Kampmeyer et al, 2023:
Lysine deserts prevent adventitious ubiquitylation of ubiquitin-proteasome components
doi.org/10.1007/s000...

CBP-IDRs regulate acetylation and gene expression. Intrinsically disordered regions (IDRs) have emerged as crucial regulators of protein function, allowing proteins to sense and respond to their environment. Creb binding protein (CBP) and EP300 (p300)...

Hot off the press for your Friday morning! 🔥 Our new (and highly revised!) preprint is out. It significantly expands on our previous work, unveiling exciting new data on how CBP's intrinsically disordered regions (IDRs) regulate genes.
Link to preprint: tinyurl.com/5npjkyps

#IDRs #condensates #CBP

Thrilled to share our new @natcomms.nature.com paper on local ancestry informed allele frequencies in gnomAD, which are live now on the browser! Check out my stellar PhD student @pragskore.bsky.social’s Bluetorial on how this brings finer detail to variant interpretation 🧬🖥️

Lead by postdoc in the lab Ruiqi Ge and in collaboration with Bob Coffey’s lab, we are happy to share rPAL-seq for rapid and sensitive sequencing based profiling of glycoRNAs @biorxivpreprint.bsky.social www.biorxiv.org/content/10.1...

Translation landscape of stress granules Cryo–electron tomography visualizes stress granules in situ, revealing their spatial interplay with translation machinery.

Translation landscape of stress granules | Science Advances

www.science.org/doi/10.1126/...

SBS 2025

Sign up for the inaugural Singapore Biosciences Symposium at SBS, NTU. We have an outstanding lineup of speakers at the intersection of plant biology and biomolecular condensates!

www.ntu.edu.sg/sbs/symposiu...

Theory of Condensate Size Control by Molecular Charge Asymmetry Biomolecular condensates are complex droplets comprising diverse molecules that interact by various mechanisms. Condensation is often driven by short-range attraction, but net charges can also mediate...

Out now in #ACSMacroLett: we demonstrate how molecular charge asymmetry can control the size of condensates! Work done in collaboration with @zwickergroup.bsky.social!!

Theory led by Chengjie Luo and simulations by @nathanieldhess.bsky.social!!

pubs.acs.org/doi/10.1021/...

Lab picture of Holehouse lab members past and present

Last week, Washington University made the perhaps questionable decision to award me tenure.

Without McdAB, CryoET shows large and disorganized aggregates of carboxysome components at the cell poles. By contrast, McdAB-expressing cells displayed fully assembled, properly sized, and unclustered carboxysomes distributed across the nucleoid region of the cell!

Long-term monitoring of a North American cheese cave reveals mechanisms and consequences of fungal adaptation Using a unique longitudinal sampling approach, Louw et al. demonstrate how a cheese-associated Penicillium population has adapted in an artisan cheese production facility in Vermont, USA. Adaptation i...

Long-term monitoring of a North American cheese cave reveals mechanisms and consequences of fungal adaptation

Penicillium solitum over 8 years in a cheese cave => green-to-white shift

@currentbiology.bsky.social from @benwolfe.bsky.social with @kellerlab.bsky.social

www.cell.com/current-biol...

👍

Over the moon to see my postdoc advisor, Prof. Lucy Shapiro, receive a Lasker Award—a brilliant salute to her decades of trail-blazing science, visionary leadership, and transformative mentorship. Congratulations!

Congratulations to Lucy Shapiro, 2025 #LaskerAward winner! – “for a 55-year career in biomedical science – honored for discovering how bacteria generate distinct daughter cells; and for exemplary leadership at the national level”
#Lasker2025 #LaskerLaureate #devbio 🧪

Major Medical Prizes Given to Cell Biology and Cystic Fibrosis Pioneers

Major Medical Prizes Given to Cell Biology and Cystic Fibrosis Pioneers www.nytimes.com/2025/09/11/h...

Flagellar gliding in choanoflagellates Freire-Delgado and Brunet discover a new mode of cell motility in choanoflagellates, the closest relatives of animals. Under mild confinement, choanoflagellate move over surfaces without cell deformat...

New short paper from our lab @currentbiology.bsky.social, in which we discover of a new mode of cell motility for choanoflagellates: flagellar gliding. www.cell.com/current-biol... - A 🧵

Evolutionary consequences of extreme climate events Simon Baeckens and Colin Donihue review case studies of rapid evolutionary change in response to extreme climate events and sketch a framework for future studies in the rapidly changing climate of the...

Extreme climate events can catalyze rapid evolutionary change! in our new Current Biology (@currentbiology.bsky.social) piece, Colin and I argue it’s time to study their evolutionary consequences systematically — beyond opportunistic observations. www.cell.com/current-biol...

QKI ensures splicing fidelity during cardiogenesis by engaging the U6 tri-snRNP to activate splicing at weak 5ʹ splice sites During organogenesis, precise pre-mRNA splicing is essential to assemble tissue architecture. Many developmentally essential exons bear weak 5'splice sites (5'SS) yet are spliced with high precision, ...

Excited to share some new work from our group - www.biorxiv.org/content/10.1...

A great collaboration with @kurianlab.bsky.social that began with how an RBP (QKI) controls cardiomyocyte function, and led to uncovering a unique mechanism of direct interaction with U6 & the tri-snRNP at weak 5'SS

QKI ensures splicing fidelity during cardiogenesis by engaging the U6 tri-snRNP to activate splicing at weak 5ʹ splice sites During organogenesis, precise pre-mRNA splicing is essential to assemble tissue architecture. Many developmentally essential exons bear weak 5'splice sites (5'SS) yet are spliced with high precision, ...

Many conserved exons in the heart and brain utilize weak 5 ′ splice sites, yet they are accurately spliced. But how? We show that splicing fidelity is actively enforced through a QKI-U6 checkpoint at the U1→U6 handover in essential cardiac genes during organogenesis.
www.biorxiv.org/content/10.1...

Balancing off-target and on-target considerations for optimized Cas9 CRISPR knockout library design The continued development of high-dimensional CRISPR screen readouts, such as single-cell RNA sequencing and high-content imaging, necessitates compact libraries to enable functional interrogation at ...

Doomscrolling pause to chat CRISPR libraries! Preprint describes our new, data-driven approach to combine on-target and off-target predictions much more intelligently for *selecting* guides, which we use to develop our newest Cas9 knockout library, Jacquere. Thread: www.biorxiv.org/content/10.1...

This work is incredible.

Plant biologist Lucia Strader joins Salk faculty to study plant growth signaling - Salk Institute for Biological Studies LA JOLLA—The Salk Institute will welcome plant biologist Lucia Strader as a new professor and holder of the Howard H. and Maryam R. Newman Chair in Plant Biology in October 2025. Strader is an interna...

The lab is moving to the Salk Institute! We are thrilled to join an inspiring community where we will continue to explore plant growth and development.

Deep gratitude for the years of support and collaboration at Duke/NCSU/UNC.

www.salk.edu/news-release...

Applicants wanted 5:
Open position for PhD Student Studying Vitro Single-molecule Transport Across Peroxisome Mimics
careers.tudelft.nl/job/Delft-Ph...

Deep Learning of Functional Perturbations from Condensate Morphology Biomolecular condensates compartmentalize the interior of living cells to spatiotemporally organize complex functions, yet linking molecular interactions within condensates to their mesoscale organiza...

I’m thrilled to share our preprint that uses deep learning to interrogate structure-function relationships in condensates! biorxiv.org/content/10.1... In here, we ask: can AI read condensate biology from pictures alone? Turns out yes... see what we discover below! 🤖🧬🖼️ (1/10)

Saturation genome editing of BRCA1 across cell types accurately resolves cancer risk Germline pathogenic BRCA1 variants predispose women to breast and ovarian cancer. Despite accumulation of functional evidence for variants in BRCA1 , over half of reported single-nucleotide variants (...

Our latest research is out today on ‪@medrxivpreprint.bsky.social:

www.medrxiv.org/content/10.1...

Saturation genome editing of BRCA1 across cell types accurately resolves cancer risk.

Led by the amazing Phoebe Dace. This one’s packed full of data, so check out the paper. Quick highlights… 🧵 1/n

I'm so honored to receive the 2025 Bruce Alberts Award for Excellence in Science Education. Thank you @ascbiology.bsky.social and I look forward to this year's annual ASCB meeting in Philly!

Biallelic variants in DNAJC7 cause familial amyotrophic lateral sclerosis with the TDP-43 pathology - Acta Neuropathologica Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive degeneration of motor neurons. ALS pathology primarily involves the failure of protein qualit...

Human DNAJC7 knockouts get ALS: link.springer.com/article/10.1...

Whole-genome sequencing of 490,640 UK Biobank participants - Nature A study reports whole-genome sequences for 490,640 participants from the UK Biobank and combines these data with phenotypic data to provide new insights into the relationship between human variation and sequence variation.

Nature research paper: Whole-genome sequencing of 490,640 UK Biobank participants

go.nature.com/46EtTyW