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Prof. Dr. J. Vanden Broeck (Animal Physiology and Neurobiology - Dept. of Biology - KU Leuven)
Molecular Developmental Physiology and Signal Transduction
My Research Team
Insect species under study
+ some other species …
Ongoing projects …
Study of ligands, receptors and their cellular signal transduction effectsNeuro-endocrine control of food intake, digestion and reproduction
Phase polyphenism in locusts (phenotypic plasticity)Mechanisms of systemic RNAi in insects
Belspo
IAP
Central themes of interest …
Central Nervous System Behaviour
EnvironmentCo ordination Endocrine systemCo-ordination Endocrine system
Growth Development
Feeding
Growth pMoulting/metamorphosis
Reproduction Ageing
Offspring
Control of feeding, digestion and reproduction
• Regulation of JH and 20E hormone synthesis ?R l f l t tid d t i hibit ?• 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, ...
Behavioural, Physiological and
solitaryPhysiological and
Developmental changesgregarious
2D DIGE Microarray-Mass
RNA2D-DIGE↓
Differential proteomics
yanalysis
↓Transcript-
i
spectrometry↓
Peptidomics
RNA interference
↓Gene Silencingp
omicsg
Phenotypic plasticity: 1 genome 2 extreme phenotypes (“phases”)
RNA interference (RNAi)
Bridge betweenSystemic effects
trigger dsRNA
Dicer
Bridge between genomics and phenomics
Cell-autonomous
RNA Induced Silencing Complex siRNAs
1. digestion
g p(RISC)
2. unwinding
target mRNA
3 bi di3. binding
4 d d ti Specific post transcriptional4. degradation Specific post-transcriptional silencing of gene expression
Molecular and cellular mode of action ?
Receptors and signal transduction
‘Functional Genomics’ and evolution of GPCRs‘Functional Genomics’ and evolution of GPCRsCharacterization 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 characteristicsMolecular and functional characteristicsComparative studies of ligand-receptor couples in insects/mammals
Structural and functional aspectsAnalysis of downstream signaling eventsAnalysis of downstream signaling eventsStudy of knockdown and mutant phenotypes
Sex Peptide Receptor is also activated by MIP-like peptides
Sex Peptide:
WEWPWNRKPTKFPIPSPNPRDKWCRLNLGPAWGGRC
- from male accessory gland- egg laying ↑
i i- receptivity ↓- feeding ↑- lifespan ↓
‘ ff t’- ‘sperm effect’
Overview of LGRs:
Human Fruit fly
Type A FSHRLH/CGR
FSH
LH, CG
dLGR1 GPA2/GPB5
TSHR TSH, Thyrostimulin (GPA2/GPB5) ( )
LGR4 unknown dLGR2 bursiconType BLGR5
LGR6
unknown
unknown
LGR7
LGR8
RLN2, RLN3
INSL3 RLN2
dLGR3
dLGR4
unknown
unknownType C
LGR8 INSL3, RLN2, RLN1
dLGR4 unknown
Thesis topics:
• Molecular genetics of G protein-coupled receptors in the fruit fly, D hil l t
Molecular genetics of signal 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
transduction in Drosophila
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
Phase transition in desert locusts
• 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
Control of reproduction + mode of action
physiology• Functional characterization of neuropeptide precursors and G
protein-coupled receptors (GPCR) involved in the regulation of feeding in the desert locust, Schistocerca gregaria Control of feeding and/or
f d di ig , g g
• The role of neuropeptides and protease inhibitors in food digestion• Protease inhibitor induced responses in pest insects• Key mechanisms of systemic RNA interference in the desert locust RNA interference !
food digestion
If you have specific questions: for each topic there is a contact person !
Many thanks for your attention! Many thanks for your attention!