scholarly journals Komagataella phaffii as Emerging Model Organism in Fundamental Research

2021 ◽  
Vol 11 ◽  
Author(s):  
Lukas Bernauer ◽  
Astrid Radkohl ◽  
Leonie Gabriela Katharina Lehmayer ◽  
Anita Emmerstorfer-Augustin

Komagataella phaffii (Pichia pastoris) is one of the most extensively applied yeast species in pharmaceutical and biotechnological industries, and, therefore, also called the biotech yeast. However, thanks to more advanced strain engineering techniques, it recently started to gain attention as model organism in fundamental research. So far, the most studied model yeast is its distant cousin, Saccharomyces cerevisiae. While these data are of great importance, they limit our knowledge to one organism only. Since the divergence of the two species 250 million years ago, K. phaffii appears to have evolved less rapidly than S. cerevisiae, which is why it remains more characteristic of the common ancient yeast ancestors and shares more features with metazoan cells. This makes K. phaffii a valuable model organism for research on eukaryotic molecular cell biology, a potential we are only beginning to fully exploit. As methylotrophic yeast, K. phaffii has the intriguing property of being able to efficiently assimilate methanol as a sole source of carbon and energy. Therefore, major efforts have been made using K. phaffii as model organism to study methanol assimilation, peroxisome biogenesis and pexophagy. Other research topics covered in this review range from yeast genetics including mating and sporulation behavior to other cellular processes such as protein secretion, lipid biosynthesis and cell wall biogenesis. In this review article, we compare data obtained from K. phaffii with S. cerevisiae and other yeasts whenever relevant, elucidate major differences, and, most importantly, highlight the big potential of using K. phaffii in fundamental research.

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Severin Sasso ◽  
Herwig Stibor ◽  
Maria Mittag ◽  
Arthur R Grossman

In the mid-20th century, the unicellular and genetically tractable green alga Chlamydomonas reinhardtii was first developed as a model organism to elucidate fundamental cellular processes such as photosynthesis, light perception and the structure, function and biogenesis of cilia. Various studies of C. reinhardtii have profoundly advanced plant and cell biology, and have also impacted algal biotechnology and our understanding of human disease. However, the 'real' life of C. reinhardtii in the natural environment has largely been neglected. To extend our understanding of the biology of C. reinhardtii, it will be rewarding to explore its behavior in its natural habitats, learning more about its abundance and life cycle, its genetic and physiological diversity, and its biotic and abiotic interactions.


2021 ◽  
Vol 10 (6) ◽  
pp. 1239
Author(s):  
Alexandru Cojocaru ◽  
Emilia Burada ◽  
Adrian-Tudor Bălșeanu ◽  
Alexandru-Florian Deftu ◽  
Bogdan Cătălin ◽  
...  

As the average age and life expectancy increases, the incidence of both acute and chronic central nervous system (CNS) pathologies will increase. Understanding mechanisms underlying neuroinflammation as the common feature of any neurodegenerative pathology, we can exploit the pharmacology of cell specific ion channels to improve the outcome of many CNS diseases. As the main cellular player of neuroinflammation, microglia play a central role in this process. Although microglia are considered non-excitable cells, they express a variety of ion channels under both physiological and pathological conditions that seem to be involved in a plethora of cellular processes. Here, we discuss the impact of modulating microglia voltage-gated, potential transient receptor, chloride and proton channels on microglial proliferation, migration, and phagocytosis in neurodegenerative diseases.


2021 ◽  
Vol 7 (2) ◽  
pp. 149
Author(s):  
Sarah-Maria Wege ◽  
Katharina Gejer ◽  
Fabienne Becker ◽  
Michael Bölker ◽  
Johannes Freitag ◽  
...  

The phytopathogenic smut fungus Ustilago maydis is a versatile model organism to study plant pathology, fungal genetics, and molecular cell biology. Here, we report several strategies to manipulate the genome of U. maydis by the CRISPR/Cas9 technology. These include targeted gene deletion via homologous recombination of short double-stranded oligonucleotides, introduction of point mutations, heterologous complementation at the genomic locus, and endogenous N-terminal tagging with the fluorescent protein mCherry. All applications are independent of a permanent selectable marker and only require transient expression of the endonuclease Cas9hf and sgRNA. The techniques presented here are likely to accelerate research in the U. maydis community but can also act as a template for genome editing in other important fungi.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Joris J. B. Messelink ◽  
Muriel C. F. van Teeseling ◽  
Jacqueline Janssen ◽  
Martin Thanbichler ◽  
Chase P. Broedersz

AbstractThe order and variability of bacterial chromosome organization, contained within the distribution of chromosome conformations, are unclear. Here, we develop a fully data-driven maximum entropy approach to extract single-cell 3D chromosome conformations from Hi–C experiments on the model organism Caulobacter crescentus. The predictive power of our model is validated by independent experiments. We find that on large genomic scales, organizational features are predominantly present along the long cell axis: chromosomal loci exhibit striking long-ranged two-point axial correlations, indicating emergent order. This organization is associated with large genomic clusters we term Super Domains (SuDs), whose existence we support with super-resolution microscopy. On smaller genomic scales, our model reveals chromosome extensions that correlate with transcriptional and loop extrusion activity. Finally, we quantify the information contained in chromosome organization that may guide cellular processes. Our approach can be extended to other species, providing a general strategy to resolve variability in single-cell chromosomal organization.


Biosensors ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 257
Author(s):  
Sebastian Fudickar ◽  
Eike Jannik Nustede ◽  
Eike Dreyer ◽  
Julia Bornhorst

Caenorhabditis elegans (C. elegans) is an important model organism for studying molecular genetics, developmental biology, neuroscience, and cell biology. Advantages of the model organism include its rapid development and aging, easy cultivation, and genetic tractability. C. elegans has been proven to be a well-suited model to study toxicity with identified toxic compounds closely matching those observed in mammals. For phenotypic screening, especially the worm number and the locomotion are of central importance. Traditional methods such as human counting or analyzing high-resolution microscope images are time-consuming and rather low throughput. The article explores the feasibility of low-cost, low-resolution do-it-yourself microscopes for image acquisition and automated evaluation by deep learning methods to reduce cost and allow high-throughput screening strategies. An image acquisition system is proposed within these constraints and used to create a large data-set of whole Petri dishes containing C. elegans. By utilizing the object detection framework Mask R-CNN, the nematodes are located, classified, and their contours predicted. The system has a precision of 0.96 and a recall of 0.956, resulting in an F1-Score of 0.958. Considering only correctly located C. elegans with an [email protected] IoU, the system achieved an average precision of 0.902 and a corresponding F1 Score of 0.906.


2001 ◽  
Vol 114 (12) ◽  
pp. 2213-2222 ◽  
Author(s):  
Martin D. Bootman ◽  
Peter Lipp ◽  
Michael J. Berridge

Calcium (Ca2+) is a ubiquitous intracellular messenger, controlling a diverse range of cellular processes, such as gene transcription, muscle contraction and cell proliferation. The ability of a simple ion such as Ca2+ to play a pivotal role in cell biology results from the facility that cells have to shape Ca2+ signals in space, time and amplitude. To generate and interpret the variety of observed Ca2+ signals, different cell types employ components selected from a Ca2+ signalling ‘toolkit’, which comprises an array of homeostatic and sensory mechanisms. By mixing and matching components from the toolkit, cells can obtain Ca2+ signals that suit their physiology. Recent studies have demonstrated the importance of local Ca2+ signals in defining the specificity of the interaction of Ca2+ with its targets. Furthermore, local Ca2+ signals are the triggers and building blocks for larger global signals that propagate throughout cells.


Author(s):  
Erina A. Balmer ◽  
Carmen Faso

Protein secretion in eukaryotic cells is a well-studied process, which has been known for decades and is dealt with by any standard cell biology textbook. However, over the past 20 years, several studies led to the realization that protein secretion as a process might not be as uniform among different cargos as once thought. While in classic canonical secretion proteins carry a signal sequence, the secretory or surface proteome of several organisms demonstrated a lack of such signals in several secreted proteins. Other proteins were found to indeed carry a leader sequence, but simply circumvent the Golgi apparatus, which in canonical secretion is generally responsible for the modification and sorting of secretory proteins after their passage through the endoplasmic reticulum (ER). These alternative mechanisms of protein translocation to, or across, the plasma membrane were collectively termed “unconventional protein secretion” (UPS). To date, many research groups have studied UPS in their respective model organism of choice, with surprising reports on the proportion of unconventionally secreted proteins and their crucial roles for the cell and survival of the organism. Involved in processes such as immune responses and cell proliferation, and including far more different cargo proteins in different organisms than anyone had expected, unconventional secretion does not seem so unconventional after all. Alongside mammalian cells, much work on this topic has been done on protist parasites, including genera Leishmania, Trypanosoma, Plasmodium, Trichomonas, Giardia, and Entamoeba. Studies on protein secretion have mainly focused on parasite-derived virulence factors as a main source of pathogenicity for hosts. Given their need to secrete a variety of substrates, which may not be compatible with canonical secretion pathways, the study of mechanisms for alternative secretion pathways is particularly interesting in protist parasites. In this review, we provide an overview on the current status of knowledge on UPS in parasitic protists preceded by a brief overview of UPS in the mammalian cell model with a focus on IL-1β and FGF-2 as paradigmatic UPS substrates.


Microbiology ◽  
2020 ◽  
Vol 166 (1) ◽  
pp. 73-84 ◽  
Author(s):  
Cristina Bez ◽  
Sree Gowrinadh Javvadi ◽  
Iris Bertani ◽  
Giulia Devescovi ◽  
Corrado Guarnaccia ◽  
...  

Azelaic acid is a dicarboxylic acid that has recently been shown to play a role in plant-bacteria signalling and also occurs naturally in several cereals. Several bacteria have been reported to be able to utilize azelaic acid as a unique source of carbon and energy, including Pseudomonas nitroreducens . In this study, we utilize P. nitroreducens as a model organism to study bacterial degradation of and response to azelaic acid. We report genetic evidence of azelaic acid degradation and the identification of a transcriptional regulator that responds to azelaic acid in P. nitroreducens DSM 9128. Three mutants possessing transposons in genes of an acyl-CoA ligase, an acyl-CoA dehydrogenase and an isocitrate lyase display a deficient ability in growing in azelaic acid. Studies on transcriptional regulation of these genes resulted in the identification of an IclR family repressor that we designated as AzeR, which specifically responds to azelaic acid. A bioinformatics survey reveals that AzeR is confined to a few proteobacterial genera that are likely to be able to degrade and utilize azelaic acid as the sole source of carbon and energy.


2007 ◽  
Vol 6 (11) ◽  
pp. 2056-2065 ◽  
Author(s):  
Ekkehard Hiller ◽  
Sonja Heine ◽  
Herwig Brunner ◽  
Steffen Rupp

ABSTRACT The SUN gene family has been defined in Saccharomyces cerevisiae and comprises a fungus-specific family of proteins which show high similarity in their C-terminal domains. Genes of this family are involved in different cellular processes, like DNA replication, aging, mitochondrial biogenesis, and cytokinesis. In Candida albicans the SUN family comprises two genes, SUN41 and SIM1. We demonstrate that C. albicans mutants lacking SUN41 show similar defects as found for S. cerevisiae, including defects in cytokinesis. In addition, the SUN41 mutant showed a higher sensitivity towards the cell wall-disturbing agent Congo red, whereas no difference was observed in the presence of calcofluor white. Compared to the wild type, SUN41 deletion strains exhibited a defect in biofilm formation, a reduced adherence on a Caco-2 cell monolayer, and were unable to form hyphae on solid medium under the conditions tested. Interestingly, Sun41p was found to be secreted in the medium of cells growing as blastospores as well as those forming hyphae. Our results support a function of SUN41p as a glycosidase involved in cytokinesis, cell wall biogenesis, adhesion to host tissue, and biofilm formation, indicating an important role in the host-pathogen interaction.


2009 ◽  
Vol 187 (5) ◽  
pp. 589-596 ◽  
Author(s):  
Karmella A. Haynes ◽  
Pamela A. Silver

Synthetic biology aims to engineer novel cellular functions by assembling well-characterized molecular parts (i.e., nucleic acids and proteins) into biological “devices” that exhibit predictable behavior. Recently, efforts in eukaryotic synthetic biology have sprung from foundational work in bacteria. Designing synthetic circuits to operate reliably in the context of differentiating and morphologically complex cells presents unique challenges and opportunities for progress in the field. This review surveys recent advances in eukaryotic synthetic biology and describes how synthetic systems can be linked to natural cellular processes in order to manipulate cell behavior and to foster new discoveries in cell biology research.


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