The main aims in our research group is to decipher mechanisms with which neurodevelopmental programs are regulated and to identify novel non-coding RNA-mediated stress response pathways.
Caenorhabditis elegans as a model system
We use the nematode C. elegans as a model system to study neuronal development and function and to decipher molecular mechanisms of non-coding RNA-mediated stress responses. Sophisticated molecular genetic techniques, ease of observation and detailed anatomical, genetic and molecular information make the worm an excellent experimental model.
There are two major focus areas of our research:
1 - Neurobiology
The C. elegans nervous system consists of just 302 neurons, the synaptic connectivity of which has been fully mapped. Such simplicity and depth of knowledge enables us to delineate molecular pathways that define the nervous system to the level of the neuronal circuit to a single neuron. Furthermore, we are able to delineate how previous experience, or genetic and environmental perturbation affects behaviour.
We use forward and reverse genetic approaches to identify genes that (1) determine neuron-type specific gene expression programs and (2) sculpt the complex architecture of the nervous system. We wish to decipher how environmental stress impinges on these developmental programs and to understand what effect such stressors have on behaviour.
2 - Non-coding RNAs
microRNAs and other non-coding regulatory RNAs have important functions in development, differentiation and disease. We are using C. elegans to better understand how ncRNAs regulate developmental processes and stress responses. C. elegans is unique in that most of the identified microRNAs in the worm have genetic knockout strains available. We are using small RNA deep sequencing technology to identify microRNAs that are regulated in response to environmental stress. We then use the microRNA knockout strains to identify specific roles of these microRNAs under stress. We have already identified specific microRNAs that are regulated by reduction in oxygen levels. Current investigations aim to elucidate the roles of these microRNAs in the response and adaptation to hypoxic insults.
Kagias K, Podolska A, Pocock R. Reliable reference miRNAs for quantitative gene expression analysis of stress responses in Caenorhabditis elegans. BMC Genomics. 2014 Mar 21;15(1):222.
Pedersen ME, Snieckute G, Kagias K, Nehammer C, Multhaupt HA, Couchman JR, Pocock R. (2013). An epidermal microRNA regulates neuronal migration through control of the cellular glycosylation state. Science. 2013 Sep 20;341(6152):1404-8
Gramstrup Petersen J, Rojo Romanos T, Juozaityte V, Redo Riveiro A, Hums I, Traunmüller L, Zimmer M, Pocock R. (2013). EGL-13/SoxD Specifies Distinct O2 and CO2 Sensory Neuron Fates in Caenorhabditis elegans. PLoS Genet. 2013 May;9(5)
Mosbech A, Gibbs-Seymour I, Kagias K, Thorslund T, Beli P, Povlsen L, Nielsen SV, Smedegaard S, Sedgwick G, Lukas C, Hartmann-Petersen R, Lukas J, Choudhary C, Pocock R, Bekker-Jensen S, Mailand N. (2012). DVC1 (C1orf124) is a DNA damage-targeting p97 adaptor that promotes ubiquitin-dependent responses to replication blocks. Nat Struct Mol Biol. 2012 Nov;19(11):1084-92.
Brandt JP, Aziz-Zaman S, Juozaityte V, Martinez-Velazquez LA, Petersen JG, Pocock R, Ringstad N. (2012). A single gene target of an ETS-family transcription factor determines neuronal CO2-chemosensitivity. PLoS One. 2012;7(3)
Pocock, R. Invited review: decoding the microRNA response to hypoxia. Pflugers Arch. 2011 Mar;461(3):307-15. Epub 2011 Jan 5.
Pocock R, Hobert O. Hypoxia activates a latent circuit for processing
gustatory information in C. elegans. Nat Neurosci. 2010 Apr 18. [Epub ahead of
Bertucci, A., Rander-Pehrson, G., Pocock, R. and Brenner, D. (2009). Microbeam irradiation of the C. elegans nematode. Journal of Radiation Research Mar; 50 Suppl A:A49-54.
Pocock, R and Hobert, O. (2008). Oxygen levels affect axon guidance and neuronal migration in Caenorhabditis elegans. Nature Neuroscience Aug; 11(8):894-900.
Pocock, R., Mione, M, Hussain, S., Maxwell, S., Pontecorvi, M., Aslam, S., Gerrelli, D., Sowden, J. and Woollard, A. (2008). Neuronal function of Tbx20 conserved from nematodes to vertebrates. Dev Biol. May 15;317(2):671-85.
Pocock, R., Benard, C. Y., Shapiro, L. and Hobert, O. (2008). Functional dissection of the C. elegans cell adhesion molecule SAX-7, a homologue of human L1. Mol Cell Neurosci. Jan;37(1):56-68.
Boulin, T., Pocock, R. and Hobert, O. (2006). A novel Eph receptor-interacting Ig/FnIII domain protein provides C.elegans motoneurons with midline guidepost function. Current Biology, 16, 1871-1883.
Pocock, R, Maxwell, S, Mitsch, M, Ahringer, J, and Woollard, A. (2004). A regulatory network of T-box genes and the even-skipped homologue vab-7 controls patterning and morphogenesis in C. elegans. Development, 131, 2373-2385.