Molecular Developmental Physiology and Signal Transduction

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1 Prof. Dr. J. Vanden Broeck (Animal Physiology and Neurobiology - Dept. of Biology - KU Leuven) Molecular Developmental Physiology and Signal Transduction

2 My Research Team

3

4 Insect species under study + some other species

5 Ongoing projects Study of ligands, receptors and their cellular signal transduction effects Neuro-endocrine control of food intake, digestion and reproduction Phase polyphenism in locusts (phenotypic plasticity) Mechanisms of systemic RNAi in insects IAP Belspo

6 Central themes of interest Central Nervous System Behaviour Environment Co-ordinationordination Endocrine system Feeding Growth Reproduction Development Moulting/metamorphosis Ageing Offspring

7 Control of feeding, digestion and reproduction Regulation of JH and 20E hormone synthesis? Role of regulatory peptides and protease inhibitors? Cloning, mrna profiling (qrt-pcr), RNAi, peptide production & purification, biological activity, regulation of vitellogenesis, egg laying, sperm production, fecundity/fertility, hormone assays, hormone biosynthesis enzymes, digestive enzyme activities,...

8 gregarious Behavioural, Physiological and Developmental changes solitary 2D-DIGEDIGE Differential proteomics Microarray- analysis Transcript- omics Mass spectrometry Peptidomics RNA interference Gene Silencing Phenotypic plasticity: 1 genome 2 extreme phenotypes ( phases )

9 RNA interference (RNAi) Bridge between genomics and phenomics Dicer trigger dsrna Systemic effects Cell-autonomous 1. digestion sirnas RNA Induced Silencing Complex (RISC) 2. unwinding target mrna 3. binding 4 d d ti Specific post transcriptional 4. degradation Specific post-transcriptional silencing of gene expression

10 Molecular and cellular mode of action?

11 Receptors and signal transduction Functional Genomics and evolution of GPCRs Characterization of ligands for receptors of interest expressed in cell lines (neuropeptides, biogenic amines, chemical libraries...) Evolutionary aspects (related GPCRs in other Metazoa) Molecular and functional characteristics Comparative studies of ligand-receptor couples in insects/mammals Structural and functional aspects Analysis of downstream signaling events Study of knockdown and mutant phenotypes

12 Sex Peptide Receptor is also activated by MIP-like peptides Sex Peptide: WEWPWNRKPTKFPIPSPNPRDKWCRLNLGPAWGGRC - from male accessory gland - egg laying - receptivity - feeding - lifespan - sperm effect

13 Overview of LGRs: Human Fruit fly Type A FSHR FSH dlgr1 GPA2/GPB5 LH/CGR LH, CG TSHR TSH, Thyrostimulin (GPA2/GPB5) Type B LGR4 unknown dlgr2 bursicon LGR5 unknown LGR6 unknown Type C LGR7 RLN2, RLN3 dlgr3 unknown LGR8 INSL3, RLN2, RLN1 dlgr4 unknown

14 Thesis topics: Molecular genetics of G protein-coupled receptors in the fruit fly, Drosophila melanogaster Molecular genetic analysis of Drosophila melanogaster leucine-rich repeats containing G protein-coupled receptors (LGRs) Neural mechanisms of swarming in locusts: a molecular approach Molecular study of factors involved in the behavioural phase transition of the desert locust, Schistocerca gregaria Control of lipophilic insect hormone biosynthesis in the desert locust Functional analysis of neuropeptide-receptor couples involved in the regulation of the reproductive physiology in the desert locust The effects of mating on female insect behaviour and reproductive physiology Functional characterization of neuropeptide precursors and G protein-coupled receptors (GPCR) involved in the regulation of feeding in the desert locust, Schistocerca gregaria g The role of neuropeptides and protease inhibitors in food digestion Molecular genetics of signal transduction in Drosophila Phase transition in desert locusts Control of reproduction + mode of action Control of feeding and/or food ddigestion i Protease inhibitor induced responses in pest insects Key mechanisms of systemic RNA interference in the desert locust RNA interference! If you have specific questions: for each topic there is a contact person!

15 Many thanks for your attention!

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