Cornelis (Cok) Johannes Pieter Grimmelikhuijzen

Research interests
My research interests are the molecular neurobiology, molecular endocrinology, and the functional and comparative genomics of invertebrates. As model systems I use two animal groups, namely cnidarians and insects.

I have chosen cnidarians, because they are the lowest animal group (phylum) with a nervous system, and because they are simple and can be used as model systems, e.g., by developmental biologists. Furthermore, cnidarians occupy a very basal position in the phylogenetic tree of animals (before the split of protostomes and deuterostomes). Cnidarians, therefore, are crucial for our understanding of the evolution of body plans and nervous systems. In cnidarians, we investigate the structure of neuropeptides, neuropeptide biosynthesis, neuropeptide receptors, and neuropeptide actions. This molecular and cellular work is basic for our understanding of the functioning of present-day cnidarians, but it also gives us insights in the evolution of the first nervous (and endocrine) systems.

Insects are the largest animal group on earth (80% of all animal species are insects). They are economically and ecologically extremely important, because most flowering plants depend on insects for their pollination. But insects can also be severe pests, destroying about 30% of our annual crop and be vectors (intermediate pathogen carriers) for serious diseases, such as malaria, sleeping sickness, Dengue fever, yellow fever, and elephantiasis. All this makes insects and the study of insects very important. At present, there are highly exciting developments occurring within the field of insect research, because the genomes from twenty-four insect species have recently been sequenced, or are in the process of being sequenced. Among these insect species are the fruitfly Drosophila melanogaster; the malaria mosquito Anopheles gambiae; the yellow fever mosquito Aedes aegypti; the honey bee Apis mellifera; the silkworm Bombyx mori; and the red flour beetle Tribolium castaneum. The genomic databases of these insects are goldmines, because they contain the information of all proteins and, thereby, of all biochemical and physiological processes that occur in an insect.

Of all proteins in insects, I am especially interested in neuropeptide receptors (which are G protein-coupled receptors) and their corresponding ligands, because these proteins (and peptides) play a central role in the physiology of insects, i.e., they occupy a high “hierarchic” position in the steering and coordination of important processes such as reproduction, development and behavior. Furthermore, G protein-coupled receptors are excellent drug targets and one of the possible applications of our basic research program might be the future development of a new specific and environmentally safe insecticide that acts selectively on a certain pest insect.

Our laboratory wants to identify and functionally characterize all major groups of neuropeptide receptors and their ligands in Drosophila and in some of the other insects with a sequenced genome. We expect that our program will drastically advance our understanding of insects, because it will give us a whole new view on insect endocrinology. The genomic sequence of each insect represents a window into insect evolution. Our project, therefore, will also give us a wealth of information on neuropeptide receptor evolution and receptor-ligand co-evolution.

Selected recent publications

Gulia-Nuss M, et al., F Hauser, C J P Grimmelikhuijzen, et al., (The Tick Genome Sequencing Consortium) (2016). Genomic insights into the Ixodes scapularis tick vector of Lyme disease. Nature Communications, 7:10507

Li S, F Hauser, SK Skadborg, SV Nielsen, N Kirketerp-Møller, C J P Grimmelikhuijzen (2016). Adipokinetic hormones and their G protein-coupled receptors emerged in Lophotrochozoa. Sci Rep 6: 32789

Kanost M R, et al., F Hauser, et al., C J P Grimmelikhuijzen, et al. (The Manduca Genome Sequencing Consortium) (2016). Multifacetted biological insights from a draft genome sequence of the tobacco hornworm Manduca sexta. Insect Biochem Mol Biol, 76:118-147

Kapheim KM, et al., F Hauser, C J P Grimmelikhuijzen, et al., J Wang, G E Robinson, G Zhang (2015). Genomic signatures of evolutionary transitions from solitary to group living. Science, 348: 1139-1143

Ren G R, F Hauser, K F Rewitz, S Kondo, A F Engelbrecht, A K Didriksen, S R Schjøtt, F E Sembach, S Li, K C Søgaard, L Søndergaard, C J P Grimmelikhuijzen (2015). CCHamide-2 is an Orexigenic Brain-Gut Peptide in Drosophila. PLoS ONE, 10: e0133017

Ren G R, J Folke, F Hauser, S Li, C J P Grimmelikhuijzen (2015). The A- and B-type muscarinic acetylcholine receptors from Drosophila melanogaster couple to different second messenger pathways. Biochem Biophys Res Commun, 462: 358-364

Sadd B M, S Barribeau, G Bloch, D C de Graaf, P Dearden, C G Elsik, J Gadau, C J P Grimmelikhuijzen, et al. (The Bumble Bee Genome Sequencing Consortium) (2015). The genomes of two key bumblebee species with primitive eusocial organization. Genome Biology 16: 76

Zhao C, et al., F Hauser, C J P Grimmelikhuijzen, et al., S Richards (The Hessian Fly Genome Sequencing Consortium) (2015). A massive expansion of effector genes underlies gall-formation in the wheat pest Mayetiola destructor. Current Biology C 25: 613-620

Chipman A, et al., F Hauser, C J P Grimmelikhuijzen, et al., S Richards (The Centipede Genome Seqencing Consortium) (2014). The first myriapod genome sequence reveals conserved arthropod gene content and genome organization in the centipede Strigamia maritima. PLoS Biology 12: e1002005

Poulsen M, H Hu, C Li, Z Chen, L Xu, S Otani, S Nygaard, T Nobre, S Klaubauf, P M Schindler, F Hauser, H Pan, Z Yang, A S Sonnenberg, Z W de Beer, Y Zhang, M J Wingfield, C J P Grimmelikhuijzen, R P de Vries, J Korp, D K Aanen, J Wang, J J Boomsma, G Zhang (2014). Complementary symbiont contributions to plant decomposition in a fungus-farming termite. Proc Natl Acad Sci USA 111:14500-14505

Hauser F, C J P Grimmelikhuijzen (2014) Evolution of the AKH/ACP/GnRH receptor superfamily and their ligands in the Protostomia. Gen Comp Endocrinol 209: 35-49 

Binzer H, CM Heuer, M Kollmann, J Kahnt, F Hauser, C J P Grimmelikhuijzen, J Schachtner (2014). The neuropeptidome of Tribolium castaneum antennal lobes and mushroom bodies. J Comp Neurol 522: 337-357

Zandawala M, S Li, F Hauser, C J P Grimmelikhuijzen, I Orchard (2013). Isolation and functional characterization of calcitonin-like diuretic hormone receptors in Rhodnius prolixus. PLoS One 8: e82466

Li S, T Torre-Muruzabal, K C Søgaard, G R Ren, F Hauser, S M Engelsen, M D Pødenphanth, A Desjardins, C J P Grimmelikhuijzen (2013). Expression patterns of the Drosophila neuropeptide CCHamide-2 and its receptor may suggest hormonal signaling from the gut to the brain. PLoS One 8: e76131

Collin C, F Hauser, E Gonzalez de Valdivia, S Li, J Reisenberger, E M M Carlsen, Z Kahn, N Ø Hansen, F Puhm, L Søndergaard, J Niemiec, M Heninger, G R Ren, C J P Grimmelikhuijzen (2013). Two types of muscarinic acetylcholine receptors in Drosophila and other arthropods. Cell Mol Life Sci 70: 3231-3242

Grimmelikhuijzen CJP, Hauser F (2012) Mini-Review: the evolution of neuropeptide signaling. Regul Pept 177 Suppl: S6-S9

Grimmelikhuijzen CJP, Hauser F (2012) Arthropod genomics and pest management targeting GPCRs. In: Advanced Technologies for Managing Insect Pests (eds. I. Ishaaya et al.), Springer Verlag, Heidelberg, pp. 165-177

Dircksen H, S Neupert, R Predel, P Verleyen, J Huybrechts, J Strauss, F Hauser, E Stafflinger, M Schneider, K Pauwels, L Schoofs, CJP Grimmelikhuijzen (2011) Genomics, transcriptomics, and peptidomics of Daphnia pulex neuropeptides and protein hormones. J Proteome Res 10: 4478-4504

Collin C, F Hauser, P Krogh-Meyer, KK Hansen, E Gonzales de Valdivia, M Williamson, CJP Grimmelikhuijzen (2011) Identification of the Drosophila and Tribolium receptors for the recently discovered insect RYamide neuropeptides. Biochem Biophys Res Commun 412: 578-583

Nygaard S, G Zhang, M Schiøtt, C Li, Y Wurm, H Hu, J Zhou, L Ji, F Qiu, M Rasmussen, H Pan, F Hauser, A Krogh, C J P Grimmelikhuijzen, J Wang, J J Boomsma (2011). The genome of the leaf-cutting ant Acromyrmex echinator suggests key adaptations to advanced social life and fungus farming. Genome Res 21: 1339-1348

Terenius O, A Papanicolaou, J S Garbutt, I Eleftherianos, H Huvenne, S Kanginakudru, M Albrechtsen, C An, J L Aymeric, A Barthel, P Bebas, K Bitra, A Bravo, F Chevalier, D P Collinge, C M Crava, R A de Maagd, B Duvic, M Erlandson, I Faye, G Felföldi, H Fujiwara, R Futahashi, A S Gandhe , H S Gatehouse, L N Gatehouse, J M Giebultowicz, I Gómez, C J P Grimmelikhuijzen, A T Groot, F Hauser, D G Heckel, D D Hegedus, S Hrycaj, L Huang, J J Hull, K Iatrou, M Iga, M R Kanost, J Kotwica, C Li, J  Li, J Liu, M Lundmark, S Matsumoto, M Meyering-Vos, P J Millichap, A Monteiro, N Mrinal, T Niimi, D Nowara, A Ohnishi, V Oostra, K Ozaki, M Papakonstantinou, A Popadic, M V Rajam, S Saenko, R M Simpson, M Soberón, M R Strand, S Tomita, U Toprak, P Wang, C W Wee, S Whyard, W Zhang, J Nagaraju, R H Ffrench-Constant, S Herrero, K Gordon, L Swevers, G Smagghe (2011). RNA interference in Lepidoptera: an overview of succesful and unsuccesful studies and implications for experimental design. J Insect Physiol 57: 231-245

Hansen KK, F Hauser, M Williamson, S B Weber, C J P Grimmelikhuijzen (2011). The Drosophila genes CG14593 and CG30106 code for G protein-coupled receptors specifically activated by the neuropeptides CCHamide-1 and CCHamide-2. Biochem Biophys Res Commun 404: 184-1899

Hauser F, S Neupert, M Williamson, R Predel, Y Tanaka and C J P Grimmelikhuijzen (2010). Genomics and peptidomics of neuropeptides an protein hormones present in the parasitic wasp Nasonia vitripennis. J Proteome Res 9: 5296-5310

Werren JH et al., C J P Grimmelikhuijzen, G Cazzamali, F Hauser, M Schneider, E Stafflinger and M Williamson et al. (Nasonia Genome Working Group) (2010). Functional and evolutionary insights from the genomes of three parasitoid Nasonia species. Science 327: 343-348

Richards S et al., C J P Grimmelikhuijzen, F Hauser, G Cazzamali, M Williamson, M Schneider, K K Hansen, and E Stafflinger et al. (The international Aphid Genomics Consortium) (2010). Genome sequence of the pea aphid Acyrthosiphon pisum. PLoS Biol 8: e1000313

Hansen K K, E Stafflinger, M Schneider, F Hauser, G Cazzamali, M Williamson and C J P Grimmelikhuijzen (2010). Discovery of a novel insect neuropeptide signaling system closely related to the insect adipokinetic hormone and corazonin hormonal systems. J Biol Chem 285: 10736-10747

Dürrnagel S, A Kuhn, C D Tsiairis, M Williamson, H Kalbacher, C J P Grimmelikhuijzen, TW Holstein and S Gründer (2010). Three homologous subunits form a high affinity peptide-gated ion channel in Hydra. J Biol Chem 285: 11958-11965

Grimmelikhuijzen C J P, G Cazzamali, M Williamson, M Schneider and F Hauser (2009). Invertebrate neurohormone GPCRs. In: Encyclopedia of Neuroscience, Volume 5 (ed. L R Squire), Academic Press, Oxford, pp. 205-212

Richards S et al., F Hauser, G Cazzamali, M Williamson and C J P Grimmelikhuijzen et al. (Tribolium castaneum Genome Sequencing Consortium) (2008). The genome sequence of the model beetle and pest Tribolium castaneum. Nature 452: 949-955

Stafflinger E ,  K K Hansen, F Hauser, M Schneider, G Cazzamali, M Williamson and C J P Grimmelikhuijzen (2008). Cloning and identification of an oxytocin/vasopressin-like receptor and its ligand from insects. Proc Natl Acad Sci USA 105: 3262-3267

Hauser F, G Cazzamali, M Williamson, Y Park, B Li, Y Tanaka, R Predel, S Neupert, J Schachtner, P Verleyen and C J P Grimmelikhuijzen (2008). A genome-wide inventory of neurohormone GPCRs in the red flour beetle Tribolium castaneum. Front Neuroendocrinol 29: 142-165

Li B, R Predel, S Neupert, F Hauser, Y Tanaka, G Cazzamali, M Williamson, Y Arakane, P Verleyen, L Schoofs, J Schachtner, C J P Grimmelikhuijzen and Y Park (2008). Genomics, transcriptomics, and peptidomics of neuropeptides and protein hormones in the red flour beetle Tribolium castaneum. Genome Res 18: 113-122

Golubovic A, A Kuhn, M Williamson, H Kalbacher, T W Holstein, C J P Grimmelikhuijzen and S Gründer (2007). A peptide-gated ion channel from the freshwater polyp Hydra. J Biol Chem 282: 35098–35103

Olsen S S, G Cazzamali, M Williamson, C J P Grimmelikhuijzen and F Hauser (2007). Identification of one capa and two pyrokinin receptors from the malaria mosquito Anopheles gambiae. Biochem Biophys Res Commun 362: 245-251

Grimmelikhuijzen C J P, G Cazzamali, M Williamson and F Hauser (2007). The promise of insect genomics. Pest Manag Sci 63: 413-416

Weinstock GM et al., F Hauser, G Cazzamali, M Williamson and C J P Grimmelikhuijzen et al. (Honey Bee Genome Sequencing Consortium) (2006). Insights into social insects from the genome of the honey bee Apis mellifera. Nature 443: 931-949

Hauser F, G Cazzamali, M Williamson, W Blenau and C J P Grimmelikhuijzen (2006). A review of neurohormone GPCRs present in the fruitfly Drosophila melanogaster and the honey bee Apis mellifera. Prog Neurobiol 80: 1-19

Belmont M, G Cazzamali, M Williamson, F Hauser and C J P Grimmelikhuijzen (2006) Identification of four evolutionarily related G protein-coupled receptors from the malaria mosquito Anopheles gambiae. Biochem Biophys Res Commun 344: 160-165

Hansen K K, F Hauser, G Cazzamali, M Williamson and C J P Grimmelikhuijzen (2006) Cloning and characterization of the adipokinetic hormone receptor from the cockroach Periplaneta americana. Biochem Biophys Res Commun 343: 638-643

Hauser F, M Williamson, G Cazzamali and C J P Grimmelikhuijzen (2006) Identifying neuropeptide and protein hormone receptors in Drosophila by exploiting genomic data. Brief Funct Genom Proteom 14: 321-330

Jørgensen L M, F Hauser, G Cazzamali, M Williamson M and C J P Grimmelikhuijzen (2006) Molecular identification of the first SIFamide receptor. Biochem Biophys Res Commun 340: 696-701

Cazzamali G, D A Klaerke and C J P Grimmelikhuijzen (2005) A new family of insect tyramine receptors. Biochem Biophys Res Commun 338: 1189-1196

Cazzamali G, M Torp, F Hauser, M Williamson and C J P Grimmelikhuijzen (2005). The Drosophila gene CG9918 codes for pyrokinin-1 receptor. Biochem Biophys Res Commun 335: 14-19

Mendive F M, T van Looy, S Claesen, J Poel, M Williamson, F Hauser, C J P Grimmelikhuijzen, G Vassart and J vanden Broeck (2005). Drosophila molting neurohormone bursicon is a heterodimer and the natural agonist of the orphan receptor DLGR2. FEBS Lett 579: 2171-2176

Schöller S, M Belmont, G Cazzamali, F Hauser, M Williamson and C J P Grimmelikhuijzen (2005). Molecular identification of a myosuppressin receptor from the malaria mosquito Anopheles gambiae. Biochem Biophys Res Commun 327: 29-34

Katsukara Y, H Ando, C N David, C J P Grimmelikhuijzen and T Sugiyama (2004). Control of planula migration by LWamide and RFamide neuropeptides in Hydractinia echinata. J Exp Biol 207: 1803-1810

Pernet V, M Anctil and C J P Grimmelikhuijzen (2004). Antho-RFmide-containing neurons in the primitive neurvous system of the anthozoan Renilla koellikeri. J Comp Neurol 472: 208-220

Egerod K, E Reynisson, F Hauser, G Cazzamali, M Williamson and C J P Grimmelikhuijzen (2003). Molecular cloning and functional expression of the first two specific insect myosuppressin receptors. Proc Natl Acad Sci USA 100: 9808-9813

Rosenkilde C, G Cazzamali, M Williamson, F Hauser, L Søndergaard, R Delotto and C J P Grimmelikhuijzen (2003). Molecular cloning, functional expression, and gene silencing of two receptors for the Drosophila neuropeptide pyrokinin-2. Biochem Biophys Res Commun 309: 485-494

Egerod K, E Reynisson, F Hauser, M Williamson, G Cazzamali and C J P Grimmelikhuijzen (2003). Molecular identification of the first insect proctolin receptor. Biochem Biophys Res Commun 306: 437-442

Katsukura Y, C N David, C J P Grimmelikhuijzen and T Sugiyama (2003). Inhibition of metamorphosis by RFamide neuropeptides in planula larvae of Hydractinia echinata. Dev Genes Evol 213: 579-586

Cazzamali G, F Hauser, S Kobberup, M Williamson and C J P Grimmelikhuijzen (2003). Molecular identification of a Drosophila G protein-coupled receptor specific for crustacean cardioactive peptide. Biochem Biophys Res Commun 303: 146-152

Cazzamali G and C J P Grimmelikhuijzen (2002). Molecular cloning and functional expression of the first insect FMRFamide receptor. Proc Natl Acad Sci USA 99:12073-12078

Staubli F, T J D Jørgensen, G Cazzamali, M Williamson, C Lenz, L Søndergaard, P Roepstorff and C J P Grimmelikhuijzen (2002). Molecular identification of the insect adipokinetic hormone receptors. Proc Natl Acad Sci USA 99: 3446-3451

Cazzamali G, NPE Saxild and C J P Grimmelikhuijzen (2002). Molecular cloning and functional expression of a Drosophila corazonin receptor. Biochem Biophys Res Commun 298: 31-36

Iversen A, G Cazzamali, M Williamson, F Hauser and C J P Grimmelikhuijzen (2002). Molecular identification of the first insect ecdysis triggering hormone receptors. Biochem Biophys Res Commun 299: 924-931

Secher T, C Lenz , G Cazzamali, G Sørensen, M Williamson, G N Hansen, P Svane and C J P Grimmelikhuijzen (2001). Molecular cloning of a functional allatostatin gut/brain receptor and an allatostatin preprohormone from the silkworm Bombyx mori. J Biol Chem 276: 47052-47060

Eriksen K , F Hauser, M Schiøtt, K-M Pedersen, L Søndergaard and C J P Grimmelikhuijzen (2000). Molecular cloning, genomic organization, developmental regulation, and a knock-out mutant of a novel Leu-rich repeats containing G protein-coupled receptor (DLGR-2) from Drosophila melanogaster. Genome Res 10: 924-938

Mitgutsch C, F Hauser and C J P Grimmelikhuijzen (1999). Expression and developmental regulation of the Hydra-RFamide and Hydra-LWamide preprohormone genes in Hydra: Evidence for transient phases of head formation. Develop Biol 207: 181-203

Activities for scientific organisations
I am an elected member of the Royal Danish Academy of Sciences and Letters since 2000, and former secretary and president (1997-2003) of the Danish Biological Society (Biologisk Selskab) in Copenhagen. I am Chairman of Cell and Neurobiology, Department of Biology, University of Copenhagen. Furthermore, I am a regular reviewer for the Deutsche Forschungsgemeinschaft (Bonn), Heisenberg Programm (Bonn), Boehringer Ingelheim Fonds (Stuttgart), Human Frontier Science Program Organisation (Strasbourg), Nederlandse Organisatie voor Wetenschappelijk Onderzoek (Den Haag), Biologisch Onderzoek Nederland (Den Haag), Stichting Levenswetenschappen (Den Haag), Swiss National Science Foundation (Bern), Fonds zur Föderung der Wissenschaftlichen Forschung (Wien), Academy of Sciences of the Czech Republic (Prague), Czech Science Foundation (Prague), Hungarian Scientific Research Fund (Budapest), Belgian Ministry of Education (Brussels), Wetenschappelijk Onderzoek Vlaanderen (Brussels), Fonds Wetenschappelijk Onderzoek (Brussels), The Wellcome Trust (London), Research Councils UK (London), Biotechnology and Biological Sciences Research Council (Swindon, UK), Research Grants Council (Hong Kong), National Science Foundation of China (Bejing), Foundation for Research Development (Pretoria), Thomson Reuters and Times Higher Education (Philadelphia), Vanderbilt University (Nashville, USA), and University of Toronto (Canada). In addition, I am reviewer for a very large number of international scientific journals, among them PNAS and Science, Reviewing Editor for Frontiers in Neuroendocrine Research, and Editor for Scientific Data (nature.com).

Research and teaching output
Publications: 186 full papers. Invited lectures on international scientific meetings and institutions: 114, see for example Session-1: https://royalsociety.org/science-events-and-lectures/2017/03/neuropeptide-signalling/

Thomson Reuters Web of Science citation index: 9703 x cited; H-index: 53. Google Scholar citation index: 12531 x cited; H-index: 61. Completed research supervision of 55 master students, 12 Ph.D. students, and 8 postdocs. I am teaching a high level course on molecular neurobiology (7½ ECTS) for about 100 students yearly, see: http://sis.ku.dk/kurser/viskursus.aspx?knr=130746

Curriculum vitae

10.12.1975
Ph.D. in biochemistry with Prof. E.C. Slater, University of Amsterdam, The Netherlands

1976-1979
Staff member at the European Laboratory for Molecular Biology (EMBL) in Heidelberg, Germany

1979-1982
Postdoc at the the Max Planck Institute for Medical Research and at the Zoological Institute, University of Heidelberg

1979-1981
Research visits at the Department of Histology, University of Lund, Sweden (Prof. F. Sundler; EMBO Short-term fellowship) and at the Department of Medical Biochemistry, University of Aarhus, Denmark (Prof. J.F. Rehfeld; EMBO Short-term fellowship)

02.06.1982
"Habilitation" and venia legendi (zoology - neurobiology) at the University of Heidelberg

01.07.1982-30.06.1987
Heisenberg-Fellow and leader of an independent research group at the Zoological Institute University of Heidelberg (the Heisenberg Fellowship is the most prestigious fellowship award in Germany)

01.07.1987-31.03.1988
Leader of a "guestgroup" at the Center for Molecular Biology, University of Heidelberg

01.04.1988-31.12.1993
Head of an independent research group at the Center for Molecular Neurobiology, University of Hamburg, Germany

09.08.1989
"Habilitation" and venia legendi (in biochemistry) at the University of Hamburg

13.05.1992
Title of "Professor" awarded by the Town of Hamburg

From 01.01.1994
Full Professor (Chairman) at the Department of Biology, University of Copenhagen, Denmark

Awards and honors

24.08.1998
Prize: "Best Biology Teacher of the Year", awarded by the University of Copenhagen

06.04.2000
Honor: Elected Member of the Royal Danish Academy of Sciences and Letters

20.11.2008
Honor: Knight of the Order of Dannebrog (Ridder af Dannebrogordenen), a royal honor awarded by the Queen of Denmark

 

 


Last updated: 13-02-2018

CORNELIS (COK) GRIMMELIKHUIJZEN
Professor

University of Copenhagen
Department of Biology
Center for Functional and Comparative Insect Genomics
Universitetsparken 15
DK-2100 Copenhagen Ø
Phone: +45 35 32 12 27
Secretary: +45 35 32 12 16
E-mail: cgrimmelikhuijzen@bio.ku.dk