Albertha J. M. Walhout (2006) "Biochemistry and molecular biology"

Albertha J. M. Walhout

[2006]

Miller DM et al. (1992) Worm Breeder's Gazette "unc-4 LacZ Expression in A-Type Motor Neurons"

Miller DM, Niemeyer CJ

[Worm Breeder's Gazette, 1992]

unc-4 LacZ expression in A-type motor neurons David M. Miller and Charles J. Niemeyer, Dept. of Cell Biology, Duke Univ. Medical Ctr, Durham, NC 27710

Ramos CG et al. (2014) J Bacteriol "Retraction for Ramos et al., MtvR is a global small noncoding regulatory RNA in Burkholderia cenocepacia."

Feliciano JR, da Costa PJ, Ramos CG, Grilo AM, Leitao JH

[J Bacteriol, 2014]

Volume 195, no. 16, p. 35143523, 2013. A number of problems related to images published in this paper have been brought to our attention. Figure 1D contains duplicated images in lanes S and LE, and Fig. 4D and 6B contain images previously published in articles in this journal and in Microbiology and Microbial Pathogenesis, i.e., the following: C. G. Ramos, S. A. Sousa, A. M. Grilo, J. R. Feliciano, and J. H. Leitao, J. Bacteriol. 193:15151526, 2011. doi:10.1128/JB.01374-11. S. A. Sousa, C. G. Ramos, L. M. Moreira, and J. H. Leitao, Microbiology 156:896908, 2010. doi:10.1099/mic.0.035139-0. C. G. Ramos, S. A. Sousa, A. M. Grilo, L. Eberl, and J. H. Leitao, Microb. Pathog. 48:168177, 2010. doi: 10.1016/j.micpath.2010.02.006. Therefore, we retract the paper. We deeply regret this situation and apologize for any inconvenience to the editors and readers of Journal of Bacteriology, Microbial Pathogenesis, and Microbiology.

Walhout AJM et al. (2000) Science "Protein interaction mapping in C. elegans using proteins involved in vulval development."

Sordella R, Hartley JL, Lu WX, Thierry-Mieg N, Walhout AJM, Brasch MA, Temple GF, Vidal MI

[Science, 2000]

Protein interaction mapping using large-scale two-hybrid analysis has been proposed as a way to functionally annotate large numbers of uncharacterized proteins predicted by complete genome sequences. This approach was examined in Caenorhabditis elegans, starting with 27 proteins involved in vulval development. The resulting map reveals both known and new potential interactions and provides a functional annotation for approximately 100 uncharacterized gene products. A protein interaction mapping project is now feasible for C. elegans on a genome-wide scale and should contribute to the understanding of molecular mechanisms in this organism and in human diseases.AD - Massachusetts General Hospital Cancer Center, Charlestown, MA 02129, USA.FAU - Walhout, A JAU - Walhout AJFAU - Sordella, RAU - Sordella RFAU - Lu, XAU - Lu XFAU - Hartley, J LAU - Hartley JLFAU - Temple, G FAU - Temple GFFAU - Brasch, M AAU - Brasch MAFAU - Thierry-Mieg, NAU - Thierry-Mieg NFAU - Vidal, MAU - Vidal MLA - engID - 1 R21 CA81658 A 01/CA/NCIID - 1 RO1 HG01715-01/HG/NHGRIPT - Journal ArticleCY - UNITED STATESTA - ScienceJID - 0404511RN - 0 (Genetic Vectors)RN - 0 (Helminth Proteins)RN - 0 (LIN-35 protein)RN - 0 (LIN-53 protein)RN - 0 (Repressor Proteins)RN - 0 (Retinoblastoma Protein)SB - IM

Welsh, Christofer M et al. (2021) International Worm Meeting "Characterization of a membrane stress response to stabilize intracellular trafficking in C. elegans"

Walker, Amy K, Bulcha, Jote T, Walhout, Albertha J M, Welsh, Christofer M

[International Worm Meeting, 2021]

Membranes form the outer boundaries of cells and their organelles. Some organelles, such as the endoplasmic reticulum (ER), mitochondria and Golgi apparatus, are defined by the structure and composition of their membranes. Dysfunction in the structure or function of membrane-defined organelles results in activation of stress responses to stabilize and restore the organelles. Organelle stress responses can affect lifespan and the aging process and may be activated in other physiological conditions such as during lipid accumulation in metabolic disease. Membrane stress responses in the ER and mitochondria can induce pathologies due to metabolic dysfunction, and as such constitute a public health concern. However, the Golgi stress response, a nascent field of study, has not been as extensively investigated. Using Caenorhabditis elegans and human cell lines, we have found that altering levels of the membrane phospholipid phosphatidylcholine (PC) changes Golgi function by inactivating a key intracellular trafficking enzyme, the small GTPase ARF-1/ARF1. Furthermore, work in our lab has shown that dysfunctional COPI retrograde as well as COPII anterograde trafficking induces upregulation of the lowly expressed warf-1/arf-1.1 in C. elegans. Additionally, our data indicates that upregulation of warf-1 is dependent on LET-607/CREB3. We hypothesize that changes in the lipid composition of the Golgi apparatus, such as reduced levels of PC, activates a dual stress response to restore lipid homeostasis by SBP-1/SREBP1 and stabilize Golgi trafficking by the compensatory WARF-1. Warf-1 is unique to C. elegans, however, in many respects its regulation and function are reminiscent of human ARF4. Like ARF4, warf-1 is upregulated in response to dysfunctional COPI retrograde trafficking by LET-607/CREB3. Furthermore, the N-terminal end of WARF-1 resembles that of ARF4 more closely than ARF1. It has been shown that this domain is required for class II ARFs to associate with ERGIC membranes during dysfunctional intracellular trafficking Consequently, investigating the warf-1 membrane stress response will enhance our understanding of how human ARF4 functions during altered membrane lipid composition and stress to intracellular trafficking.

Wang, Juan et al. (2017) International Worm Meeting "Biogenesis and Function of Social Extracellular Vesicles (EVs)."

Barr, Maureen, Wang, Juan, Silva, Malan

[International Worm Meeting, 2017]

Extracellular vesicles are emerging as an important aspect of intercellular communication by delivering a parcel of proteins, lipids even nucleic acids to specific target cells over short or long distances (Maas 2017). A subset of C. elegans ciliated neurons release EVs to the environment and elicit changes in male behaviors in a cargo-dependent manner (Wang 2014, Silva 2017). Our studies raise many questions regarding these social communicating EV devices. Why is the cilium the donor site? What mechanisms control ciliary EV biogenesis? How are bioactive functions encoded within EVs? EV detection is a challenge and obstacle because of their small size (100nm). However, we possess the first and only system to visualize and monitor GFP-tagged EVs in living animals in real time. We are using several approaches to define the properties of an EV-releasing neuron (EVN) and to decipher the biology of ciliary-released EVs. To identify mechanisms regulating biogenesis, release, and function of ciliary EVs we took an unbiased transcriptome approach by isolating EVNs from adult worms and performing RNA-seq. We identified 335 significantly upregulated genes, of which 61 were validated by GFP reporters as expressed in EVNs (Wang 2015). By characterizing components of this EVN parts list, we discovered new components and pathways controlling EV biogenesis, EV shedding and retention in the cephalic lumen, and EV environmental release. We also identified cell-specific regulators of EVN ciliogenesis and are currently exploring mechanisms regulating EV cargo sorting. Our genetically tractable model can make inroads where other systems have not, and advance frontiers of EV knowledge where little is known. Maas, S. L. N., Breakefield, X. O., & Weaver, A. M. (2017). Trends in Cell Biology. Silva, M., Morsci, N., Nguyen, K. C. Q., Rizvi, A., Rongo, C., Hall, D. H., & Barr, M. M. (2017). Current Biology. Wang, J., Kaletsky, R., Silva, M., Williams, A., Haas, L. A., Androwski, R. J., Landis JN, Patrick C, Rashid A, Santiago-Martinez D, Gravato-Nobre M, Hodgkin J, Hall DH, Murphy CT, Barr, M. M. (2015).Current Biology. Wang, J., Silva, M., Haas, L. A., Morsci, N. S., Nguyen, K. C. Q., Hall, D. H., & Barr, M. M. (2014). Current Biology.

Tatiana Akimkina et al. (2002) European Worm Meeting "Genome organization of Microbacterium nematophilum and possible determinants and mechanisms involved in pathogenicity for C. elegans"

Jonathan Hodgkin, Steve Curnock, Tatiana Akimkina

[European Worm Meeting, 2002]

M. nematophilum is a novel pathogen of C. elegans recently described by J. Hodgkin et al. (1). The bacterium is able to attach to the post-anal region of C. elegans and to induce massive swelling of the underlying tissues by an unknown mechanism. The disease causes constipation and slows growth of affected worms. M. nematophilum belongs to the Gram-positive coryneform group of bacteria and is poorly characterised.

Foehr ML et al. (2008) Dev Biol "Dorsoventral patterning of the C. elegans postembryonic mesoderm requires both LIN-12/Notch and TGFbeta signaling."

Liu J, Foehr ML

[Dev Biol, 2008]

The C. elegans postembryonic mesodermal lineage arises from a single cell M, which generates distinct dorsal and ventral cell types. We have previously shown that mutations in the Schnurri homolog sma-9 cause ventralization of the M lineage and that wild-type SMA-9 antagonizes the Sma/Mab TGFbeta pathway to promote dorsal M lineage fates [Foehr, M.L., Lindy, A.S., Fairbank, R.C., Amin, N.M., Xu, M., Yanowitz, J., Fire, A.Z., Liu, J., 2006. An antagonistic role for the C. elegans Schnurri homolog SMA-9 in modulating TGFbeta signaling during mesodermal patterning. Development 133, 2887-2896]. Interestingly, loss-of-function mutations in the Notch receptor lin-12 cause dorsalization of the M lineage [Greenwald, I.S., Sternberg, P.W., Horvitz, H.R., 1983. The lin-12 locus specifies cell fates in Caenorhabditis elegans. Cell 34, 435-444]. We have found that although LIN-12 protein is present in both the dorsal and ventral M lineage cells, its ligands LAG-2 and APX-1 are asymmetrically localized in cells adjacent to ventral M-derived cells, and may function redundantly in promoting ventral M lineage fates. To investigate how LIN-12/Notch signaling interacts with SMA-9 and Sma/Mab TGFbeta signaling in regulating M lineage patterning, we generated double and triple mutant combinations among lin-12, sma-9 and dbl-1 (the ligand for the Sma/Mab TGFbeta pathway) and examined their M lineage phenotypes. Our results suggest that the LIN-12/Notch pathway and the Sma/Mab TGFbeta pathway function independently in regulating dorsoventral patterning of the M lineage, with LIN-12/Notch required for ventral M lineage fates, and SMA-9 antagonism of TGFbeta signaling required for dorsal M lineage fates. Our work provides a model for how combined Notch and TGFbeta signaling regulates the developmental potential of two equipotent cells along the dorsoventral axis.

Li, C.C.Y. et al. (2017) International Worm Meeting "Towards a unified global C. elegans Metabolic Reconstruction Model."

Li, C.C.Y., Witting, M., Kaleta, C., Casanueva, O, Hastings, J., Le Novere, N.

[International Worm Meeting, 2017]

C. elegans has recently been advanced as a premier metazoan model organism for the study of metabolism, with the publication of two whole-genome metabolic models (1, 2). Using these models together with -omics data allows the in-depth data-driven exploration of systems-level metabolism using in silico simulations. In a GENiE workshop to be held April 2017 at the Babraham Institute, Cambridge, UK, the relationships between these two existing metabolic models will be explored with the objective of generating a consensus model. Because the two reconstructions are still incomplete, and certain important pathways and areas of metabolism are currently under-annotated, we aim to identify specific areas that are relevant to the C. elegans community and prioritise them for further annotation in a follow-up community-driven "annotation jamboree" workshop. This poster will describe the main objectives set by the first workshop and opens the invitation to the C. elegans metabolic research community to contribute to the follow-up annotation efforts. 1. Gebauer, J.; Gentsch, C.; Mansfeld, J.; Schmei beta er, K.; Waschina, S.; Brandes, S.; Klimmasch, L.; Zamboni, N.; Zarse, K.; Schuster, S.; Ristow, M.; Schauble, S. & Kaleta, C. (2016), 'A Genome-Scale Database and Reconstruction of Caenorhabditis elegans Metabolism.', Cell Syst 2(5), 312--322. 2. Yilmaz, L. S. & Walhout, A. J. M. (2016), 'A Caenorhabditis elegans Genome-Scale Metabolic Network Model.', Cell Syst 2(5), 297--311.

Von Stetina, Stephen E. et al. (2009) International Worm Meeting "Finding Regulators of Cadherin-Independent Epithelialization."

Mango, Susan E., Von Stetina, Stephen E.

[International Worm Meeting, 2009]

How are polarized epithelia established and maintained? This question is of critical importance, as the loss of epithelial polarity is associated with metastasis(1). There are many well-studied protein complexes that lie in specific membrane compartments with roles integral to the epithelial cell. The E-cadherin-containing adherens junction serves to link neighboring epithelial cells together while the more basal tight junction functions to separate the apical and basolateral surfaces. For some cells, E-cadherin is the major initiator of cell polarity and epithelium formation via cell-cell adhesion(2). However, recent studies have discovered E-cadherin independent polarity pathways(3-6). C. elegans offers a powerful system to study this cadherin-independent mechanism, as E-cadherin is dispensible for the initiation of epithelial polarity in nematodes(4). We study cadherin-independent epithelium formation during pharynx development. Nine pharyngeal arcade cells undergo a mesenchymal-to-epithelial transition to link the pharynx to the outer epidermis(7). Ablation of the arcade cells results in a Pharynx unattached (Pun) phenotype, in which the pharynx fails to connect to the epidermis(7). Pun animals die as they are unable to eat. Our lab has undertaken a genetic screen for Pun mutants that fail to form the arcade cell epithelium (Portereiko and Mango, unpublished). This screen revealed that loss of the central-spindlin component ZEN-4/MKLP1 induces a Pun phenotype because the arcade cells fail to polarize(8). We are currently studying where and when ZEN-4 is needed for arcade cell polarization. We have also undertaken a structure/function analysis of this mitotic kinesin in order to elucidate its role in epithelialization. In addition, we are in the process of cloning several mutants that were isolated in the Pun mutagenesis screen. (1). J. M. Lee, S. Dedhar, R. Kalluri, E. W. Thompson, J Cell Biol 172, 973 (Mar 27, 2006). (2). L. N. Nejsum, W. J. Nelson, J Cell Biol 178, 323 (Jul 16, 2007). (3). A. F. Baas et al., Cell 116, 457 (Feb 6, 2004). (4). M. Costa et al., J Cell Biol 141, 297 (Apr 6, 1998). (5). T. J. Harris, M. Peifer, J Cell Biol 167, 135 (Oct 11, 2004). (6). W. B. Raich, C. Agbunag, J. Hardin, Curr Biol 9, 1139 (Oct 21, 1999). (7). M. F. Portereiko, S. E. Mango, Dev Biol 233, 482 (May 15, 2001). (8). M. F. Portereiko, J. Saam, S. E. Mango, Curr Biol 14, 932 (Jun 8, 2004).