Emerson F et al. (2020) Elife "A memory of longevity."

Lee SS, Li CL, Emerson F

[Elife, 2020]

Worms with increased levels of the epigenetic mark H3K9me2 have a longer lifespan that can be passed down to future generations.

Campbell, Richard et al. (2017) International Worm Meeting "Quantitative genetic mapping of difference in oxygen and carbon dioxide-evoked behaviors that are dependent on environmental growth conditions."

Lowder, Mark, McGrath, Patrick, Campbell, Richard

[International Worm Meeting, 2017]

The basis of behavioral variation in populations of animals is rooted in genetic, environmental and neuronal diversity. Since C. elegans is amenable to controlling each of these factors, we are seeking to understand how environmental and genetic diversity gives rise to natural differences in behaviors. Wild isolate strains such as the Hawaiian strain, CB4856, are very sensitive to small changes in atmospheric O2 and CO2 and exhibit a robust increase in turning and increase in speed in response to a shift from 20% O2/1% CO2 to 21% O2/0% CO2. Interestingly, this behavior is dependent on environmental growth conditions. If animals are grown on uniform lawns lacking an O2 gradient this response disappears. We asked if these O2 and CO2 responses are similar across different wild isolates. We found that there was variation among a representative panel of 12 wild isolates with some strains showing robust responses and some showing little to no change. To understand the genetic basis for this variation in O2 and CO2 behaviors, we are taking two approaches. First, we will perform QTL mapping on recombinant inbred lines we generated between MY14 (which does not show the sharp change in speed and turning behavior) and a modified N2 strain that contains the ancestral alleles of npr-1 and glb-5 (which shows the sharp change and speed and turning behavior. We will also perform GWAS on a large panel of wild isolates collected and sequenced by the CeNDR resource. We anticipate finding causal variants in other loci that are responsible for growth-dependent O2 and CO2 behaviors.

Wu Y et al. (2017) Curr Top Dev Biol "Regulation of Cell Polarity by PAR-1/MARK Kinase."

Wu Y, Griffin EE

[Curr Top Dev Biol, 2017]

PAR-1/MARK kinases are conserved serine/threonine kinases that are essential regulators of cell polarity. PAR-1/MARK kinases localize and function in opposition to the anterior PAR proteins to control the asymmetric distribution of factors in a wide variety polarized cells. In this review, we discuss the mechanisms that control the localization and activity of PAR-1/MARK kinases, including their antagonistic interactions with the anterior PAR proteins. We focus on the role PAR-1 plays in the asymmetric division of the Caenorhabditis elegans zygote, in the establishment of the anterior/posterior axis in the Drosophila oocyte and in the control of microtubule dynamics in mammalian neurons. In addition to conserved aspects of PAR-1 biology, we highlight the unique ways in which PAR-1 acts in these distinct cell types to orchestrate their polarization. Finally, we review the connections between disruptions in PAR-1/MARK function and Alzheimer's disease and cancer.

Benecke M et al. (1994) Worm Breeder's Gazette "DNA Fingerprinting in C. elegans - An Approach."

Epplen JT, Schierenberg E, Benecke M

[Worm Breeder's Gazette, 1994]

DNA fingerprinting in C. elegans - an approach Mark Beneckea, Jorg T. Epplenb and Einhard Schierenberga a Zoologisches Institut der Univeritat, 50923 Koln, Germany b Ruhr-Universitat, Ab1. fur Molekulare Humangenetik, 44780 Bochum, Germany

Butkevich E et al. (2016) Sci Rep "Phosphorylation of FEZ1 by Microtubule Affinity Regulating Kinases regulates its function in presynaptic protein trafficking."

Grosche J, Erck C, Urlaub H, Nikolov M, Klopfenstein DR, Butkevich E, Chua JJ, Hartig W, Schmidt CF

[Sci Rep, 2016]

Adapters bind motor proteins to cargoes and therefore play essential roles in Kinesin-1 mediated intracellular transport. The regulatory mechanisms governing adapter functions and the spectrum of cargoes recognized by individual adapters remain poorly defined. Here, we show that cargoes transported by the Kinesin-1 adapter FEZ1 are enriched for presynaptic components and identify that specific phosphorylation of FEZ1 at its serine 58 regulatory site is mediated by microtubule affinity-regulating kinases (MARK/PAR-1). Loss of MARK/PAR-1 impairs axonal transport, with adapter and cargo abnormally co-aggregating in neuronal cell bodies and axons. Presynaptic specializations are markedly reduced and distorted in FEZ1 and MARK/PAR-1 mutants. Strikingly, abnormal co-aggregates of unphosphorylated FEZ1, Kinesin-1 and its putative cargoes are present in brains of transgenic mice modelling aspects of Alzheimer's disease, a neurodegenerative disorder exhibiting impaired axonal transport and altered MARK activity. Our findings suggest that perturbed FEZ1-mediated synaptic delivery of proteins arising from abnormal signalling potentially contributes to the process of neurodegeneration.

Skourti-Stathaki K et al. (2013) Mol Cell "Histone 3 s10 phosphorylation: "caught in the R loop!"."

Skourti-Stathaki K, Proudfoot NJ

[Mol Cell, 2013]

In this issue of Molecular Cell, Castellano-Pozo etal. (2013) describe a connection between R loop structures and histone 3 S10 phosphorylation (H3S10P), a mark of chromatin compaction. Their results constitute asignificant advance in our understanding of the role of R loops in genomic instability.

Bohdanowicz M et al. (2010) Curr Biol "Vesicular traffic: a Rab SANDwich."

Bohdanowicz M, Grinstein S

[Curr Biol, 2010]

The small GTPases Rab5 and Rab7 mark temporally distinct but sequentially connected stages in phagosome maturation, but the mechanism underlying the transition between these stages has been unclear. Recent studies in Caenorhabditis elegans have now uncovered a new protein complex that connects Rab5 to Rab7.

Hope IA (2001) Trends Genet "Broadcast interference - functional genomics."

Hope IA

[Trends Genet, 2001]

Four recent papers mark a major shift in functional genomic analysis for multicellular organisms. RNA-mediated interference was applied to inactivate individual genes systematically on a genomic scale. These studies subjected a third of the genes in the genome of Caenorhabditis elegans to reverse genetic analysis.

(1990) Worm Breeder's Gazette "CGC Bibliography in FileMaker and HyperCard (Mac) and Memory Mate ( IBM)"

[Worm Breeder's Gazette, 1990]

The CGC Bibliography has been translated into a couple of programs other than dBase by various worm people. David Barker and Andy Fire both have sent HyperCard versions to the CGC and Mark Blaxter has sent us a version in FileMaker 2.0. None of these is perfectly up-to-date, so you'll have to be somewhat familiar with the programs to add new references. The data files are available free from the CGC; to get yours, just send a blank 3.5' diskette to Mark Edgley at the CGC with a request letter. In addition, Lew Jacobson has translated the bibliography into a DOS program called Memory Mate and he is willing to distribute the data file to anyone who sends him a blank 5.25' 360 Kb diskette. Memory Mate can be operated as a TSR and called up with a hotkey from the middle of a word processor or other program. Addresses for Mark and Lew can be found in the Subscriber Directory Update in this issue.

Folkmann AW et al. (2019) Development "Spatial regulation of the polarity kinase PAR-1 by parallel inhibitory mechanisms."

Folkmann AW, Seydoux G

[Development, 2019]

The MARK/PAR-1 family of kinases are conserved regulators of cell polarity that share a conserved C-terminal kinase-associated domain (KA1). Localization of MARK/PAR-1 kinases to specific regions of the cell cortex is a hallmark of polarized cells. In <i>C. elegans</i> zygotes, PAR-1 localizes to the posterior cortex under the influence of another polarity kinase, aPKC/PKC-3. Here we report that asymmetric localization of PAR-1 protein is not essential, and that PAR-1 kinase activity is also regulated spatially. We find that, as in human MARK1, the PAR-1 KA1 domain is an auto-inhibitory domain that suppresses kinase activity. Auto-inhibition by the KA1 domain functions in parallel with phosphorylation by PKC-3 to suppress PAR-1 activity in the anterior cytoplasm. The KA1 domain also plays an additional role essential for germ plasm maintenance and fertility. Our findings suggest that modular regulation of kinase activity by redundant inhibitory inputs contributes to robust symmetry breaking by MARK/PAR-1 kinases in diverse cell types.