Special Issue "Humanized Yeast Models"

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Microbial Genetics and Genomics".

Deadline for manuscript submissions: 15 January 2020.

Special Issue Editors

Prof. Victor J. Cid
E-Mail Website
Guest Editor
Dpto. de Microbiología y Parasitología, Universidad Complutense de Madrid. Madrid, Spain.
Interests: Saccharomyces cerevisiae; yeast; signaling; heterologous expression; phosphoinositides; Toll-like receptors (TLR signaling); Phosphatidylinositol 3.kinase (PI3K); Supramolecular organizing complexes (SMOCs)
Prof. Faustino Mollinedo
E-Mail Website
Guest Editor
Laboratory of Cell Death and Cancer Therapy, Department of Molecular Biomedicine, Centro de Investigaciones Biológicas (CIB), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain.
Interests: Lipid rafts; cell death; cell death receptors; cell signaling; anticancer drugs; antileishmanial drugs; alkylphospholipid analogs; cancer; neutrophil; Leishmania

Special Issue Information

Dear Colleagues,

Unicellular eukaryotes, like budding yeast Saccharomyces cerevisiae and fission yeast Schizosaccharomyces pombe, are consolidated models in basic research. Their genetic tractability and ease of manipulation pushed these microorganisms to a leading position in the post-genomic era, providing key information on the molecular mechanisms that govern conserved cellular modules, pathways and functions, like metabolism, cell division, signaling, vesicle traffic, cytoskeleton, aging, autophagy, etc. Furthermore, the human proteins expressed in these models are often capable of supporting the function or their yeast counterparts. Thus, heterologous expression in yeast is a powerful strategy to address the structure–function relationship in human gene products that may either stand as important drug targets or relate to pathological syndromes.

In the last two decades, multiple humanized yeast models have been developed with various purposes, either by complementing yeast mutants with human genes or by implementing functions or pathways in yeast that are naturally missing in lower eukaryotes. The formation of amyloid bodies or prion fibrils like those produced in neurons in degenerative disorders, the biosynthetic pathway of cholesterol, or oncogenic signaling pathways, to mention some examples, have been successfully reproduced in yeast. In these systems, the yeast cell provides an “in vivo test tube” that allows us to study the behavior of human proteins in the absence of other input characteristic of higher cells, but yet within a cellular environment. Typically, humanized yeast models can be exploited to design bioassays for pharmacological screens in drug discovery or to carry out exhaustive mutational analyses in order to assess protein–protein interactions, mechanistic features of enzymes or diverse functional aspects of the target proteins.

This Special Issue will cover research on the design, implementation or exploitation of yeast-based models to study human proteins, based on their heterologous expression coupled to the genetic versatility of yeast models, with emphasis on those strategies aimed at basic or applied research into genes and proteins related to human pathologies. We encourage researchers working in the field to contribute with original research or review articles.

Prof. Victor J. Cid
Prof. Faustino Mollinedo
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Genes is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Heterologous expression
  • Saccharomyces cerevisiae
  • Cell signaling
  • Apoptosis
  • Aging
  • Cancer
  • Drug discovery
  • Protein–protein interactions
  • Microbial models

Published Papers (3 papers)

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Research

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Open AccessArticle
A Humanized Yeast Phenomic Model of Deoxycytidine Kinase to Predict Genetic Buffering of Nucleoside Analog Cytotoxicity
Genes 2019, 10(10), 770; https://doi.org/10.3390/genes10100770 - 30 Sep 2019
Abstract
Knowledge about synthetic lethality can be applied to enhance the efficacy of anticancer therapies in individual patients harboring genetic alterations in their cancer that specifically render it vulnerable. We investigated the potential for high-resolution phenomic analysis in yeast to predict such genetic vulnerabilities [...] Read more.
Knowledge about synthetic lethality can be applied to enhance the efficacy of anticancer therapies in individual patients harboring genetic alterations in their cancer that specifically render it vulnerable. We investigated the potential for high-resolution phenomic analysis in yeast to predict such genetic vulnerabilities by systematic, comprehensive, and quantitative assessment of drug–gene interaction for gemcitabine and cytarabine, substrates of deoxycytidine kinase that have similar molecular structures yet distinct antitumor efficacy. Human deoxycytidine kinase (dCK) was conditionally expressed in the Saccharomyces cerevisiae genomic library of knockout and knockdown (YKO/KD) strains, to globally and quantitatively characterize differential drug–gene interaction for gemcitabine and cytarabine. Pathway enrichment analysis revealed that autophagy, histone modification, chromatin remodeling, and apoptosis-related processes influence gemcitabine specifically, while drug–gene interaction specific to cytarabine was less enriched in gene ontology. Processes having influence over both drugs were DNA repair and integrity checkpoints and vesicle transport and fusion. Non-gene ontology (GO)-enriched genes were also informative. Yeast phenomic and cancer cell line pharmacogenomics data were integrated to identify yeast–human homologs with correlated differential gene expression and drug efficacy, thus providing a unique resource to predict whether differential gene expression observed in cancer genetic profiles are causal in tumor-specific responses to cytotoxic agents. Full article
(This article belongs to the Special Issue Humanized Yeast Models)
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Review

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Open AccessReview
Sneaking Out for Happy Hour: Yeast-Based Approaches to Explore and Modulate Immune Response and Immune Evasion
Genes 2019, 10(9), 667; https://doi.org/10.3390/genes10090667 - 31 Aug 2019
Abstract
Many pathogens (virus, bacteria, fungi, or parasites) have developed a wide variety of mechanisms to evade their host immune system. The budding yeast Saccharomyces cerevisiae has successfully been used to decipher some of these immune evasion strategies. This includes the cis-acting mechanism [...] Read more.
Many pathogens (virus, bacteria, fungi, or parasites) have developed a wide variety of mechanisms to evade their host immune system. The budding yeast Saccharomyces cerevisiae has successfully been used to decipher some of these immune evasion strategies. This includes the cis-acting mechanism that limits the expression of the oncogenic Epstein–Barr virus (EBV)-encoded EBNA1 and thus of antigenic peptides derived from this essential but highly antigenic viral protein. Studies based on budding yeast have also revealed the molecular bases of epigenetic switching or recombination underlying the silencing of all except one members of extended families of genes that encode closely related and highly antigenic surface proteins. This mechanism is exploited by several parasites (that include pathogens such as Plasmodium, Trypanosoma, Candida, or Pneumocystis) to alternate their surface antigens, thereby evading the immune system. Yeast can itself be a pathogen, and pathogenic fungi such as Candida albicans, which is phylogenetically very close to S. cerevisiae, have developed stealthiness strategies that include changes in their cell wall composition, or epitope-masking, to control production or exposure of highly antigenic but essential polysaccharides in their cell wall. Finally, due to the high antigenicity of its cell wall, yeast has been opportunistically exploited to create adjuvants and vectors for vaccination. Full article
(This article belongs to the Special Issue Humanized Yeast Models)
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Open AccessReview
Yeast as a Tool for Deeper Understanding of Human Manganese-Related Diseases
Genes 2019, 10(7), 545; https://doi.org/10.3390/genes10070545 - 17 Jul 2019
Abstract
The biological importance of manganese lies in its function as a key cofactor for numerous metalloenzymes and as non-enzymatic antioxidant. Due to these two essential roles, it appears evident that disturbed manganese homeostasis may trigger the development of pathologies in humans. In this [...] Read more.
The biological importance of manganese lies in its function as a key cofactor for numerous metalloenzymes and as non-enzymatic antioxidant. Due to these two essential roles, it appears evident that disturbed manganese homeostasis may trigger the development of pathologies in humans. In this context, yeast has been extensively used over the last decades to gain insight into how cells regulate intra-organellar manganese concentrations and how human pathologies may be related to disturbed cellular manganese homeostasis. This review first summarizes how manganese homeostasis is controlled in yeast cells and how this knowledge can be extrapolated to human cells. Several manganese-related pathologies whose molecular mechanisms have been studied in yeast are then presented in the light of the function of this cation as a non-enzymatic antioxidant or as a key cofactor of metalloenzymes. In this line, we first describe the Transmembrane protein 165-Congenital Disorder of Glycosylation (TMEM165-CDG) and Friedreich ataxia pathologies. Then, due to the established connection between manganese cations and neurodegeneration, the Kufor–Rakeb syndrome and prion-related diseases are finally presented. Full article
(This article belongs to the Special Issue Humanized Yeast Models)
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