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Article ; Online: Regionalized Cell Division during Sea Urchin Gastrulation Contributes to Archenteron Formation and Is Correlated with the Establishment of Larval Symmetry: (sea urchin/gastrulation/cell division/autoradiography).

Nislow, Corey / Morrill, John B

2023 Volume 30, Issue 5, Page(s) 483–499

Abstract: During gastrulation of the sea urchin, Lytechinus variegutus there is localized proliferation of cells in the vegetal plate region prior to its invagination. Cell counts show that during gastrulation the number of cells per embryo increases 60% from 1025 ...

Abstract	During gastrulation of the sea urchin, Lytechinus variegutus there is localized proliferation of cells in the vegetal plate region prior to its invagination. Cell counts show that during gastrulation the number of cells per embryo increases 60% from 1025 to 1640. Measurements of cell volumes suggest that some growth may follow these divisions. Feulgen staining shows that the greatest mitotic activity throughout gastrulation occurs in the vegetal plate region. Labelling embryos with 3H-thymidine reveals that incorporation in the vegetal plate is confined to cells that encircle the base of the archenteron. Pulse-chase experiments indicate that these labelled cells contribute descendants to the vegetal half of the archenteron. Additionally, 3-dimensional reconstructions of vegetal regions at different stages reveal that by the end of gastrulation two bilateral clusters of labelled cells lie at the future sites of the post-oral arms of the pluteus larva, thus marking the axes of bilateral and dorso-ventral symmetry. Our findings suggest that two of the principal events of sea urchin gastrulation - the formation of the archenteron and the establishment of symmetry in the larva - are accompanied by distinct patterns of cell division.
Language	English
Publishing date	2023-06-06
Publishing country	Japan
Document type	Journal Article
ZDB-ID	280433-5
ISSN	1440-169X ; 0012-1592
ISSN (online)	1440-169X
ISSN	0012-1592
DOI	10.1111/j.1440-169X.1988.00483.x
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Article ; Online: The Addis Ababa Lions: Whole-Genome Sequencing of a Rare and Precious Population.

Barazandeh, Marjan / Kriti, Divya / Fickel, Jörns / Nislow, Corey

Genome biology and evolution

2024 Volume 16, Issue 2

Abstract: Lions are widely known as charismatic predators that once roamed across the globe, but their populations have been greatly affected by environmental factors and human activities over the last 150 yr. Of particular interest is the Addis Ababa lion ... ...

Abstract	Lions are widely known as charismatic predators that once roamed across the globe, but their populations have been greatly affected by environmental factors and human activities over the last 150 yr. Of particular interest is the Addis Ababa lion population, which has been maintained in captivity at around 20 individuals for over 75 yr, while many wild African lion populations have become extinct. In order to understand the molecular features of this unique population, we conducted a whole-genome sequencing study on 15 Addis Ababa lions and detected 4.5 million distinct genomic variants compared with the reference African lion genome. Using functional annotation, we identified several genes with mutations that potentially impact various traits such as mane color, body size, reproduction, gastrointestinal functions, cardiovascular processes, and sensory perception. These findings offer valuable insights into the genetics of this threatened lion population.
MeSH term(s)	Animals ; Humans ; Lions/genetics ; Ethiopia ; Genome
Language	English
Publishing date	2024-02-01
Publishing country	England
Document type	Journal Article
ZDB-ID	2495328-3
ISSN	1759-6653 ; 1759-6653
ISSN (online)	1759-6653
ISSN	1759-6653
DOI	10.1093/gbe/evae021
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Article ; Online: From beer to breadboards: yeast as a force for biological innovation.

Gaikani, Hamid Kian / Stolar, Monika / Kriti, Divya / Nislow, Corey / Giaever, Guri

Genome biology

2024 Volume 25, Issue 1, Page(s) 10

Abstract: The history of yeast Saccharomyces cerevisiae, aka brewer's or baker's yeast, is intertwined with our own. Initially domesticated 8,000 years ago to provide sustenance to our ancestors, for the past 150 years, yeast has served as a model research subject ...

Abstract	The history of yeast Saccharomyces cerevisiae, aka brewer's or baker's yeast, is intertwined with our own. Initially domesticated 8,000 years ago to provide sustenance to our ancestors, for the past 150 years, yeast has served as a model research subject and a platform for technology. In this review, we highlight many ways in which yeast has served to catalyze the fields of functional genomics, genome editing, gene-environment interaction investigation, proteomics, and bioinformatics-emphasizing how yeast has served as a catalyst for innovation. Several possible futures for this model organism in synthetic biology, drug personalization, and multi-omics research are also presented.
MeSH term(s)	Saccharomyces cerevisiae/genetics ; Beer
Language	English
Publishing date	2024-01-04
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2040529-7
ISSN	1474-760X ; 1474-760X
ISSN (online)	1474-760X
ISSN	1474-760X
DOI	10.1186/s13059-023-03156-9
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Article ; Online: From beer to breadboards

Hamid Kian Gaikani / Monika Stolar / Divya Kriti / Corey Nislow / Guri Giaever

Genome Biology, Vol 25, Iss 1, Pp 1-

yeast as a force for biological innovation

2024 Volume 30

Abstract: Abstract The history of yeast Saccharomyces cerevisiae, aka brewer’s or baker’s yeast, is intertwined with our own. Initially domesticated 8,000 years ago to provide sustenance to our ancestors, for the past 150 years, yeast has served as a model ... ...

Abstract	Abstract The history of yeast Saccharomyces cerevisiae, aka brewer’s or baker’s yeast, is intertwined with our own. Initially domesticated 8,000 years ago to provide sustenance to our ancestors, for the past 150 years, yeast has served as a model research subject and a platform for technology. In this review, we highlight many ways in which yeast has served to catalyze the fields of functional genomics, genome editing, gene–environment interaction investigation, proteomics, and bioinformatics—emphasizing how yeast has served as a catalyst for innovation. Several possible futures for this model organism in synthetic biology, drug personalization, and multi-omics research are also presented.
Keywords	Biology (General) ; QH301-705.5 ; Genetics ; QH426-470
Language	English
Publishing date	2024-01-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
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Article ; Online: The cellular response to drug perturbation is limited: comparison of large-scale chemogenomic fitness signatures.

Barazandeh, Marjan / Kriti, Divya / Nislow, Corey / Giaever, Guri

BMC genomics

2022 Volume 23, Issue 1, Page(s) 197

Abstract: Background: Chemogenomic profiling is a powerful approach for understanding the genome-wide cellular response to small molecules. First developed in Saccharomyces cerevisiae, chemogenomic screens provide direct, unbiased identification of drug target ... ...

Abstract	Background: Chemogenomic profiling is a powerful approach for understanding the genome-wide cellular response to small molecules. First developed in Saccharomyces cerevisiae, chemogenomic screens provide direct, unbiased identification of drug target candidates as well as genes required for drug resistance. While many laboratories have performed chemogenomic fitness assays, few have been assessed for reproducibility and accuracy. Here we analyze the two largest independent yeast chemogenomic datasets comprising over 35 million gene-drug interactions and more than 6000 unique chemogenomic profiles; the first from our own academic laboratory (HIPLAB) and the second from the Novartis Institute of Biomedical Research (NIBR). Results: Despite substantial differences in experimental and analytical pipelines, the combined datasets revealed robust chemogenomic response signatures, characterized by gene signatures, enrichment for biological processes and mechanisms of drug action. We previously reported that the cellular response to small molecules is limited and can be described by a network of 45 chemogenomic signatures. In the present study, we show that the majority of these signatures (66%) are also found in the companion dataset, providing further support for their biological relevance as conserved systems-level, small molecule response systems. Conclusions: Our results demonstrate the robustness of chemogenomic fitness profiling in yeast, while offering guidelines for performing other high-dimensional comparisons including parallel CRISPR screens in mammalian cells.
MeSH term(s)	Animals ; Drug Resistance ; Reproducibility of Results ; Saccharomyces cerevisiae/genetics
Language	English
Publishing date	2022-03-11
Publishing country	England
Document type	Journal Article
ZDB-ID	2041499-7
ISSN	1471-2164 ; 1471-2164
ISSN (online)	1471-2164
ISSN	1471-2164
DOI	10.1186/s12864-022-08395-x
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Article ; Online: Genome-wide screen identifies new set of genes for improved heterologous laccase expression in Saccharomyces cerevisiae.

Strawn, Garrett / Wong, Ryan W K / Young, Barry P / Davey, Michael / Nislow, Corey / Conibear, Elizabeth / Loewen, Christopher J R / Mayor, Thibault

Microbial cell factories

2024 Volume 23, Issue 1, Page(s) 36

Abstract: The yeast Saccharomyces cerevisiae is widely used as a host cell for recombinant protein production due to its fast growth, cost-effective culturing, and ability to secrete large and complex proteins. However, one major drawback is the relatively low ... ...

Abstract	The yeast Saccharomyces cerevisiae is widely used as a host cell for recombinant protein production due to its fast growth, cost-effective culturing, and ability to secrete large and complex proteins. However, one major drawback is the relatively low yield of produced proteins compared to other host systems. To address this issue, we developed an overlay assay to screen the yeast knockout collection and identify mutants that enhance recombinant protein production, specifically focusing on the secretion of the Trametes trogii fungal laccase enzyme. Gene ontology analysis of these mutants revealed an enrichment of processes including vacuolar targeting, vesicle trafficking, proteolysis, and glycolipid metabolism. We confirmed that a significant portion of these mutants also showed increased activity of the secreted laccase when grown in liquid culture. Notably, we found that the combination of deletions of OCA6, a tyrosine phosphatase gene, along with PMT1 or PMT2, two genes encoding ER membrane protein-O-mannosyltransferases involved in ER quality control, and SKI3, which encode for a component of the SKI complex responsible for mRNA degradation, further increased secreted laccase activity. Conversely, we also identified over 200 gene deletions that resulted in decreased secreted laccase activity, including many genes that encode for mitochondrial proteins and components of the ER-associated degradation pathway. Intriguingly, the deletion of the ER DNAJ co-chaperone gene SCJ1 led to almost no secreted laccase activity. When we expressed SCJ1 from a low-copy plasmid, laccase secretion was restored. However, overexpression of SCJ1 had a detrimental effect, indicating that precise dosing of key chaperone proteins is crucial for optimal recombinant protein expression. This study offers potential strategies for enhancing the overall yield of recombinant proteins and provides new avenues for further research in optimizing protein production systems.
MeSH term(s)	Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae/metabolism ; Laccase/genetics ; Laccase/metabolism ; Trametes/genetics ; Trametes/metabolism ; Recombinant Proteins ; Protein Processing, Post-Translational
Chemical Substances	Laccase (EC 1.10.3.2) ; Recombinant Proteins
Language	English
Publishing date	2024-01-29
Publishing country	England
Document type	Journal Article
ZDB-ID	2091377-1
ISSN	1475-2859 ; 1475-2859
ISSN (online)	1475-2859
ISSN	1475-2859
DOI	10.1186/s12934-024-02298-0
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Article ; Online: Chemical-Genetic Interactions as a Means to Characterize Drug Synergy.

Gaikani, Hamid / Giaever, Guri / Nislow, Corey

Methods in molecular biology (Clifton, N.J.)

2021 Volume 2381, Page(s) 243–263

Abstract: The combination of model organisms and comprehensive genome-wide screens has provided a wealth of data into the structure and regulation of the genome, gene-environment interactions, and more recently, into the mechanism of action of human therapeutics. ... ...

Abstract	The combination of model organisms and comprehensive genome-wide screens has provided a wealth of data into the structure and regulation of the genome, gene-environment interactions, and more recently, into the mechanism of action of human therapeutics. The success of these studies relies, in part, on the ability to quantify the combined effects of multifactorial biological interactions. In this review, we explore the history and rationale behind genetic and chemical-genetic interactions with an emphasis on the phenomena of drug synergy and then briefly describe the theoretical models that we can leverage to investigate the synergy between compounds. In addition to reviewing the literature, we also provide a reference list including many of the most important studies in this field. The concept of chemical genetics interactions derives from classical studies of synthetic lethality and functional genomics. These techniques have recently graduated from the research lab to the clinic, and a better understanding of the basic principles can help accelerate this translation.
MeSH term(s)	Gene-Environment Interaction ; Genome ; Genomics ; Humans ; Pharmaceutical Preparations ; Synthetic Lethal Mutations
Chemical Substances	Pharmaceutical Preparations
Language	English
Publishing date	2021-09-30
Publishing country	United States
Document type	Journal Article ; Review
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-1740-3_14
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Article: Pharmacogenomic Testing: Clinical Evidence and Implementation Challenges.

Hippman, Catriona / Nislow, Corey

Journal of personalized medicine

2019 Volume 9, Issue 3

Abstract: Pharmacogenomics can enhance patient care by enabling treatments tailored to genetic make-up and lowering risk of serious adverse events. As of June 2019, there are 132 pharmacogenomic dosing guidelines for 99 drugs and pharmacogenomic information is ... ...

Abstract	Pharmacogenomics can enhance patient care by enabling treatments tailored to genetic make-up and lowering risk of serious adverse events. As of June 2019, there are 132 pharmacogenomic dosing guidelines for 99 drugs and pharmacogenomic information is included in 309 medication labels. Recently, the technology for identifying individual-specific genetic variants (genotyping) has become more accessible. Next generation sequencing (NGS) is a cost-effective option for genotyping patients at many pharmacogenomic loci simultaneously, and guidelines for implementation of these data are available from organizations such as the Clinical Pharmacogenetics Implementation Consortium (CPIC) and the Dutch Pharmacogenetics Working Group (DPWG). NGS and related technologies are increasing knowledge in the research sphere, yet rates of genomic literacy remain low, resulting in a widening gap in knowledge translation to the patient. Multidisciplinary teams-including physicians, nurses, genetic counsellors, and pharmacists-will need to combine their expertise to deliver optimal pharmacogenomically-informed care.
Language	English
Publishing date	2019-08-07
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662248-8
ISSN	2075-4426
ISSN	2075-4426
DOI	10.3390/jpm9030040
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Article ; Online: A genome-wide portrait of pervasive drug contaminants.

Ogbede, Joseph Uche / Giaever, Guri / Nislow, Corey

Scientific reports

2021 Volume 11, Issue 1, Page(s) 12487

Abstract: Using a validated yeast chemogenomic platform, we characterized the genome-wide effects of several pharmaceutical contaminants, including three N-nitrosamines (NDMA, NDEA and NMBA), two related compounds (DMF and 4NQO) and several of their metabolites. A ...

Abstract	Using a validated yeast chemogenomic platform, we characterized the genome-wide effects of several pharmaceutical contaminants, including three N-nitrosamines (NDMA, NDEA and NMBA), two related compounds (DMF and 4NQO) and several of their metabolites. A collection of 4800 non-essential homozygous diploid yeast deletion strains were screened in parallel and the strain abundance was quantified by barcode sequencing. These data were used to rank deletion strains representing genes required for resistance to the compounds to delineate affected cellular pathways and to visualize the global cellular effects of these toxins in an easy-to-use searchable database. Our analysis of the N-nitrosamine screens uncovered genes (via their corresponding homozygous deletion mutants) involved in several evolutionarily conserved pathways, including: arginine biosynthesis, mitochondrial genome integrity, vacuolar protein sorting and DNA damage repair. To investigate why NDMA, NDEA and DMF caused fitness defects in strains lacking genes of the arginine pathway, we tested several N-nitrosamine metabolites (methylamine, ethylamine and formamide), and found they also affected arginine pathway mutants. Notably, each of these metabolites has the potential to produce ammonium ions during their biotransformation. We directly tested the role of ammonium ions in N-nitrosamine toxicity by treatment with ammonium sulfate and we found that ammonium sulfate also caused a growth defect in arginine pathway deletion strains. Formaldehyde, a metabolite produced from NDMA, methylamine and formamide, and which is known to cross-link free amines, perturbed deletion strains involved in chromatin remodeling and DNA repair pathways. Finally, co-administration of N-nitrosamines with ascorbic or ferulic acid did not relieve N-nitrosamine toxicity. In conclusion, we used parallel deletion mutant analysis to characterize the genes and pathways affected by exposure to N-nitrosamines and related compounds, and provide the data in an accessible, queryable database.
MeSH term(s)	Arginine/biosynthesis ; Biosynthetic Pathways/drug effects ; Biosynthetic Pathways/genetics ; DNA Damage/drug effects ; DNA Repair/drug effects ; DNA, Fungal/drug effects ; DNA, Fungal/isolation & purification ; Drug Contamination ; Genetic Fitness/drug effects ; Genome, Fungal/drug effects ; Mitochondria/drug effects ; Mitochondria/metabolism ; Nitrosamines/toxicity ; Saccharomyces cerevisiae/drug effects ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae/growth & development ; Saccharomyces cerevisiae/metabolism ; Sequence Deletion ; Toxicity Tests, Acute
Chemical Substances	DNA, Fungal ; Nitrosamines ; Arginine (94ZLA3W45F)
Language	English
Publishing date	2021-06-14
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-91792-1
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Article ; Online: Pharmacogenomic Testing

Catriona Hippman / Corey Nislow

Journal of Personalized Medicine, Vol 9, Iss 3, p

Clinical Evidence and Implementation Challenges

2019 Volume 40

Abstract	Pharmacogenomics can enhance patient care by enabling treatments tailored to genetic make-up and lowering risk of serious adverse events. As of June 2019, there are 132 pharmacogenomic dosing guidelines for 99 drugs and pharmacogenomic information is included in 309 medication labels. Recently, the technology for identifying individual-specific genetic variants (genotyping) has become more accessible. Next generation sequencing (NGS) is a cost-effective option for genotyping patients at many pharmacogenomic loci simultaneously, and guidelines for implementation of these data are available from organizations such as the Clinical Pharmacogenetics Implementation Consortium (CPIC) and the Dutch Pharmacogenetics Working Group (DPWG). NGS and related technologies are increasing knowledge in the research sphere, yet rates of genomic literacy remain low, resulting in a widening gap in knowledge translation to the patient. Multidisciplinary teams—including physicians, nurses, genetic counsellors, and pharmacists—will need to combine their expertise to deliver optimal pharmacogenomically-informed care.
Keywords	pharmacogenomics ; clinical guidelines ; implementation ; drugs ; medications ; review ; Medicine ; R
Language	English
Publishing date	2019-08-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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