David Botstein
Princeton University
H-index: 190
North America-United States
Description
David Botstein, With an exceptional h-index of 190 and a recent h-index of 70 (since 2020), a distinguished researcher at Princeton University, specializes in the field of Genetics.
His recent articles reflect a diverse array of research interests and contributions to the field:
Regulators of health and lifespan extension in genetically diverse mice on dietary restriction
Global analysis of the yeast knockout phenome
Interactions between the gut microbiome, dietary restriction, and aging in genetically diverse mice
Novel insights from a multiomics dissection of the Hayflick limit
Revisiting the hayflick limit: insights from an integrated analysis of changing transcripts, proteins, metabolites and chromatin
Loss of major nutrient sensing and signaling pathways suppresses starvation lethality in electron transport chain mutants
A genome‐scale yeast library with inducible expression of individual genes
Perspective: Linkage Maps, Communities of Geneticists, and Genome Databases
Professor Information
University | Princeton University |
---|---|
Position | ___ |
Citations(all) | 287502 |
Citations(since 2020) | 51479 |
Cited By | 257757 |
hIndex(all) | 190 |
hIndex(since 2020) | 70 |
i10Index(all) | 463 |
i10Index(since 2020) | 243 |
University Profile Page | Princeton University |
Research & Interests List
Genetics
Top articles of David Botstein
Regulators of health and lifespan extension in genetically diverse mice on dietary restriction
Caloric restriction (CR) delays aging and extends healthy lifespan in multiple species. Alternative forms of dietary restriction (DR) such as intermittent fasting (IF) have drawn significant interest as a more sustainable regimen, but the landscape of longevity-promoting dietary interventions remains largely unexplored. Identifying the most robust, efficacious, and experimentally tractable modes of DR is key to better understanding and implementing effective longevity interventions for human healthspan. To that end, we have performed an extensive assessment of DR interventions, investigating the effects of graded levels of CR (20% and 40%) and IF (1 day and 2 days of fasting per week) on the health and survival of 960 genetically diverse female mice. All interventions extended lifespan, although only CR significantly reduced the mortality doubling time. Notably, IF did not extend lifespan in mice with high pre-intervention bodyweight. We carried out extensive phenotyping to determine the health effects of long-term DR and to better understand the mechanisms driving within-diet heterogeneity in lifespan. The top within-diet predictor of lifespan was the ability of mice to maintain bodyweight through periods of handling, an indicator of stress resilience. Additional predictors of long lifespan include specific changes in immune cells, red blood cell distribution width (RDW), and retention of adiposity in late life. We found that lifespan is heritable (h 2= 0.24), and that genetic background has a larger influence on lifespan than dietary interventions. We identified a significant association for lifespan and RDW on chromosome 18 that explained 4.3% of the diet …
Authors
Gary Churchill,Andrea Di Francesco,Andrew Deighan,Lev Litichevskiy,Zhenghao Chen,Alison Luciano,Laura Robinson,Gaven Garland,Hannah Donato,Will Schott,Kevin Wright,Anil Raj,GV Prateek,Martin Mullis,Warren Hill,Mark Zeidel,Luanne Peters,Fiona Harding,David Botstein,Ron Korstanje,Christoph Thaiss,Adam Freund
Published Date
2024/1/8
Global analysis of the yeast knockout phenome
Genome-wide phenotypic screens in the budding yeast Saccharomyces cerevisiae, enabled by its knockout collection, have produced the largest, richest, and most systematic phenotypic description of any organism. However, integrative analyses of this rich data source have been virtually impossible because of the lack of a central data repository and consistent metadata annotations. Here, we describe the aggregation, harmonization, and analysis of ~14,500 yeast knockout screens, which we call Yeast Phenome. Using this unique dataset, we characterized two unknown genes (YHR045W and YGL117W) and showed that tryptophan starvation is a by-product of many chemical treatments. Furthermore, we uncovered an exponential relationship between phenotypic similarity and intergenic distance, which suggests that gene positions in both yeast and human genomes are optimized for function.
Authors
Gina Turco,Christie Chang,Rebecca Y Wang,Griffin Kim,Emily H Stoops,Brianna Richardson,Vanessa Sochat,Jennifer Rust,Rose Oughtred,Nathaniel Thayer,Fan Kang,Michael S Livstone,Sven Heinicke,Mark Schroeder,Kara J Dolinski,David Botstein,Anastasia Baryshnikova
Journal
Science Advances
Published Date
2023/5/26
Interactions between the gut microbiome, dietary restriction, and aging in genetically diverse mice
The intestinal microbiome changes with age, but the causes and consequences of microbiome aging remain unclear. Furthermore, the gut microbiome has been proposed to mediate the benefit of lifespan-extending interventions such as dietary restriction, but this hypothesis warrants further exploration. Here, by analyzing 2997 metagenomes collected longitudinally from 913 deeply phenotyped, genetically diverse mice, we provide new insights into the interplay between the microbiome, aging, dietary restriction, host genetics, and a wide range of health parameters. First, we find that microbiome uniqueness increases with age across datasets and species. Moreover, age-associated changes are better explained by cumulative exposure to stochastic events (neutral theory) than by the influence of an aging host (selection theory). Second, we unexpectedly find that the majority of microbiome features are significantly heritable and that the amount of variation explained by host genetics is as large as that of aging and dietary restriction. Third, we find that the intensity of dietary restriction parallels the extent of microbiome changes and that dietary restriction does not rejuvenate the microbiome. Lastly, we find that the microbiome is significantly associated with multiple health parameters - including body composition, immune parameters, and frailty - but not with lifespan. In summary, this large and multifaceted study sheds light on the factors influencing the microbiome and aspects of host physiology modulated by the microbiome.
Authors
Lev Litichevskiy,Maya Considine,Jasleen Gill,Vasuprada Shandar,Timothy O Cox,Helene C Descamps,Kevin M Wright,Kevin R Amses,Lenka Dohnalova,Megan J Liou,Monika Tetlak,Mario R Galindo-Fiallos,Andrea C Wong,Patrick Lundgren,Junwon Kim,Giulia T Uhr,Ryan J Rahman,Sydney Mason,Carter Merenstein,Frederic D Bushman,Anil Raj,Fiona Harding,Zhenghao Chen,GV Prateek,Martin Mullis,Andrew G Deighan,Laura Robinson,Ceylan Tanes,Kyle Bittinger,Meenakshi Chakraborty,Ami S Bhatt,Hongzhe Li,Ian Barnett,Emily R Davenport,Karl W Broman,Robert L Cohen,David Botstein,Adam Freund,Andrea Di Francesco,Gary A Churchill,Mingyao Li,Christoph A Thaiss
Journal
bioRxiv
Published Date
2023
Novel insights from a multiomics dissection of the Hayflick limit
The process wherein dividing cells exhaust proliferative capacity and enter into replicative senescence has become a prominent model for cellular aging in vitro. Despite decades of study, this cellular state is not fully understood in culture and even much less so during aging. Here, we revisit Leonard Hayflick’s original observation of replicative senescence in WI-38 human lung fibroblasts equipped with a battery of modern techniques including RNA-seq, single-cell RNA-seq, proteomics, metabolomics, and ATAC-seq. We find evidence that the transition to a senescent state manifests early, increases gradually, and corresponds to a concomitant global increase in DNA accessibility in nucleolar and lamin associated domains. Furthermore, we demonstrate that senescent WI-38 cells acquire a striking resemblance to myofibroblasts in a process similar to the epithelial to mesenchymal transition (EMT) that is regulated by t YAP1/TEAD1 and TGF-β2. Lastly, we show that verteporfin inhibition of YAP1/TEAD1 activity in aged WI-38 cells robustly attenuates this gene expression program.
Authors
Michelle Chan,Han Yuan,Ilya Soifer,Tobias M Maile,Rebecca Y Wang,Andrea Ireland,Jonathon J O'Brien,Jérôme Goudeau,Leanne JG Chan,Twaritha Vijay,Adam Freund,Cynthia Kenyon,Bryson D Bennett,Fiona E McAllister,David R Kelley,Margaret Roy,Robert L Cohen,Arthur D Levinson,David Botstein,David G Hendrickson
Journal
Elife
Published Date
2022/2/4
Revisiting the hayflick limit: insights from an integrated analysis of changing transcripts, proteins, metabolites and chromatin
Replicative senescence (RS) as a model has become the central focus of research into cellular aging in vitro. Despite decades of study, this process through which cells cease dividing is not fully understood in culture, and even much less so in vivo during development and with aging. Here, we revisit Hayflick’s original observation of RS in WI-38 human fetal lung fibroblasts equipped with a battery of high dimensional modern techniques and analytical methods to deeply profile the process of RS across each aspect of the central dogma and beyond. We applied and integrated RNA-seq, proteomics, metabolomics, and ATAC-seq to a high resolution RS time course. We found that the transcriptional changes that underlie RS manifest early, gradually increase, and correspond to a concomitant global increase in accessibility in nucleolar and lamin associated domains. During RS WI-38 fibroblast gene expression patterns acquire a striking resemblance to those of myofibroblasts in a process similar to the epithelial to mesenchymal transition (EMT). This observation is supported at the transcriptional, proteomic, and metabolomic levels of cellular biology. In addition, we provide evidence suggesting that this conversion is regulated by the transcription factors YAP1/TEAD1 and the signaling molecule TGF-β2.
Authors
Michelle Chan,Han Yuan,Ilya Soifer,Tobias M Maile,Rebecca Y Wang,Andrea Ireland,Jonathon O’Brien,Jérôme Goudeau,Leanne Chan,Twaritha Vijay,Adam Freund,Cynthia Kenyon,Bryson Bennett,Fiona McAllister,David R Kelley,Margaret Roy,Robert L Cohen,Arthur D Levinson,David Botstein,David G Hendrickson
Journal
Biorxiv
Published Date
2021/5/4
Loss of major nutrient sensing and signaling pathways suppresses starvation lethality in electron transport chain mutants
The electron transport chain (ETC) is a well-studied and highly conserved metabolic pathway that produces ATP through generation of a proton gradient across the inner mitochondrial membrane coupled to oxidative phosphorylation. ETC mutations are associated with a wide array of human disease conditions and to aging-related phenotypes in a number of different organisms. In this study, we sought to better understand the role of the ETC in aging using a yeast model. A panel of ETC mutant strains that fail to survive starvation was used to isolate suppressor mutants that survive. These suppressors tend to fall into major nutrient sensing and signaling pathways, suggesting that the ETC is involved in proper starvation signaling to these pathways in yeast. These suppressors also partially restore ETC-associated gene expression and pH homeostasis defects, though it remains unclear whether these phenotypes …
Authors
Alisha G Lewis,Robert Caldwell,Jason V Rogers,Maria Ingaramo,Rebecca Y Wang,Ilya Soifer,David G Hendrickson,R Scott McIsaac,David Botstein,Patrick A Gibney
Journal
Molecular Biology of the Cell
Published Date
2021/12/1
A genome‐scale yeast library with inducible expression of individual genes
The ability to switch a gene from off to on and monitor dynamic changes provides a powerful approach for probing gene function and elucidating causal regulatory relationships. Here, we developed and characterized YETI (Yeast Estradiol strains with Titratable Induction), a collection in which > 5,600 yeast genes are engineered for transcriptional inducibility with single‐gene precision at their native loci and without plasmids. Each strain contains SGA screening markers and a unique barcode, enabling high‐throughput genetics. We characterized YETI using growth phenotyping and BAR‐seq screens, and we used a YETI allele to identify the regulon of Rof1, showing that it acts to repress transcription. We observed that strains with inducible essential genes that have low native expression can often grow without inducer. Analysis of data from eukaryotic and prokaryotic systems shows that native expression is a …
Authors
Yuko Arita,Griffin Kim,Zhijian Li,Helena Friesen,Gina Turco,Rebecca Y Wang,Dale Climie,Matej Usaj,Manuel Hotz,Emily H Stoops,Anastasia Baryshnikova,Charles Boone,David Botstein,Brenda J Andrews,R Scott McIsaac
Journal
Molecular Systems Biology
Published Date
2021/6
Perspective: Linkage Maps, Communities of Geneticists, and Genome Databases
The Thomas Hunt Morgan Medal recognizes lifetime contributions to the field of genetics. The 2020 recipient is David Botstein of Calico Labs and Princeton University, recognizing his multiple contributions to genetics, including the collaborative development of methods for defining genetic pathways, mapping genomes, and analyzing gene expression.
Authors
David Botstein
Journal
Genetics
Published Date
2020/10/1
Professor FAQs
What is David Botstein's h-index at Princeton University?
The h-index of David Botstein has been 70 since 2020 and 190 in total.
What are David Botstein's top articles?
The articles with the titles of
Regulators of health and lifespan extension in genetically diverse mice on dietary restriction
Global analysis of the yeast knockout phenome
Interactions between the gut microbiome, dietary restriction, and aging in genetically diverse mice
Novel insights from a multiomics dissection of the Hayflick limit
Revisiting the hayflick limit: insights from an integrated analysis of changing transcripts, proteins, metabolites and chromatin
Loss of major nutrient sensing and signaling pathways suppresses starvation lethality in electron transport chain mutants
A genome‐scale yeast library with inducible expression of individual genes
Perspective: Linkage Maps, Communities of Geneticists, and Genome Databases
...
are the top articles of David Botstein at Princeton University.
What are David Botstein's research interests?
The research interests of David Botstein are: Genetics
What is David Botstein's total number of citations?
David Botstein has 287,502 citations in total.