Duronio RJ et al. (2017), Sophisticated lessons from simple organisms: ap...

ECB-ART-45952

Dis Model Mech 2017 Dec 19;1012:1381-1389. doi: 10.1242/dmm.031203.

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Sophisticated lessons from simple organisms: appreciating the value of curiosity-driven research.

Duronio RJ , O'Farrell PH , Sluder G , Su TT .

Abstract
For hundreds of years, biologists have studied accessible organisms such as garden peas, sea urchins collected at low tide, newt eggs, and flies circling rotten fruit. These organisms help us to understand the world around us, attracting and inspiring each new generation of biologists with the promise of mystery and discovery. Time and time again, what we learn from such simple organisms has emphasized our common biological origins by proving to be applicable to more complex organisms, including humans. Yet, biologists are increasingly being tasked with developing applications from the known, rather than being allowed to follow a path to discovery of the as yet unknown. Here, we provide examples of important lessons learned from research using selected non-vertebrate organisms. We argue that, for the purpose of understanding human disease, simple organisms cannot and should not be replaced solely by human cell-based culture systems. Rather, these organisms serve as powerful discovery tools for new knowledge that could subsequently be tested for conservation in human cell-based culture systems. In this way, curiosity-driven biological research in simple organisms has and will continue to pay huge dividends in both the short and long run for improving the human condition.

PubMed ID: 29259023
PMC ID: PMC5769611
Article link: Dis Model Mech
Grant support: [+]

Genes referenced: LOC100887844 LOC115919910 LOC579470

Article Images: [+] show captions

	Fig. 1. The basis for a genetic screen for budding-yeast cell-cycle mutants. (A) A genetic screen in yeast. Mutagenized yeast cells are cultured on replica plates. One plate is incubated at the low temperature to allow growth, whereas the other is incubated at a high temperature. Conditional mutants that fail to grow at the high temperature (arrows) are thus selected against when the plates are incubated at the high temperature. Microscopic analysis of the high-temperature plate identifies conditional mutants that are blocked in the cell cycle. These mutants, which retain the ability to grow at low temperature, are then isolated from the low-temperature plate for subsequent analysis, which includes complementation tests with wild-type genes to identify the gene responsible for the phenotype (Forsburg, 2001). (B) A budding-yeast cell cycle, modified from Hartwell et al., 1970, 1973. A mother cell produces a daughter by growing a bud that enlarges and eventually separates from the mother. Different stages of the cell cycle can be scored by the shape and size of the cells. For instance, the onset of DNA replication corresponds to the emergence of a bud. Mutants in CDC28, encoding the major cyclin-dependent kinase, arrest with a ‘small bud’, unable to enter a new cell cycle.
	Fig. 2. Drosophila mutants to illustrate landmark studies. (A,B) Wild-type (A) and Notch mutant (B) wings showing notched (arrow) wing blades. Figure reproduced from Casso et al., 2011, with copyright permission from the publisher. (C,D) Sex combs on the front legs of a male D. melanogaster (arrows in C) are magnified in D. In polycomb mutants, anterior/posterior patterning is disrupted, resulting in sex combs appearing also on the middle and hind legs. Reproduced under a Creative Commons license from Wikicommons and with permission from http://flymove.uni-muenster.de. See also Weigmann et al., 2003. (E,F) Suppression of eye color variegation, from Qi et al., 2006. Variegation of eye color (F; juxtaposition of patches of white and red) is suppressed in heterozygotes of a mutation in Su(var)3-9, a gene that encodes an enzyme that methylates lysine 9 of histone H3 (E; uniformly red). TM3 is a balancer chromosome and serves as a ‘wild type’ control. Reproduced with copyright permission from the publisher.
	Fig. 3. C. elegans cell-lineage map and multi-vulva mutants. (A) Experiment and data that led to the discovery of RNAi, summarized from Fire et al., 1998. (B) Cell-lineage map of C. elegans. Reproduced under a Creative Commons license from Kimble and Seidel, 2013. (C,D) Wild-type and multi-vulva (Muv) mutant worms. * indicates the vulva; arrows point to ectopic vulvae. Figures modified and reproduced under a Creative Commons license from de la Cova and Greenwald, 2012. Specification of the vulval fate occurs through Ras/MAPK signaling (Kornfeld, 1997; Sundaram and Han, 1996). Mutants in which this pathway is misregulated can show the Muv phenotype (e.g. Gu et al., 1998), which led to the discovery of regulators of Ras/MAPK signaling.

References [+] :

Aagaard, Functional mammalian homologues of the Drosophila PEV-modifier Su(var)3-9 encode centromere-associated proteins which complex with the heterochromatin component M31. 1999, Pubmed