Marek Jindra lab
of developmental genetics
- June 2021: Matěj defends his Master degree and joins the team for a Ph.D. project.
- May 2021: We publish an invited review A decade with the juvenile hormone receptor in Adv Insect Physiol with a cover illustration https://doi.org/10.1016/bs.aiip.2021.03.001
- April 2021: Raveendra Babu joins the team as a postdoc.
- February 2020: Šárka Tůmová joins the team, replacing Helena Líbalová.
- November 2019: Marek awarded the EXPRO research grant in collaboration with David Sedlák of the CZ-OPENSCREEN national infrastructure for chemical biology.
- October 2019: Matěj Miláček joins the team.
- September 2019: Lenka and Marek publish a review The juvenile hormone receptor as a target of juvenoid "insect growth regulators" in Arch Insect Biochem Physiol https://doi.org/10.1002/arch.21615
- July 2019: Marek publishes invited review "Where did the pupa come from? The timing of juvenile hormone signalling supports homology between stages of hemimetabolous and holometabolous insects" in Phil Trans R Soc B 374: 20190064. https://doi.org/10.1098/rstb.2019.0064
- July 2019: Marek co-organizes the 8th International Symposium on Molecular Insect Science in Sitges
- January 2019: Lenka published her first paper in Marek's lab, "Exquisite ligand stereoselectivity of a Drosophila juvenile hormone receptor contrasts with its broad agonist repertoire" in J Biol Chem
- October 2017: Marek awarded by the Czech Academy of Sciences for outstanding results of great scientific significance ("Discovery of juvenile hormone receptor")
- July 2017: Marek elected the Karlson Lecturer of the International Insect Hormone Workshop, Japan
Our laboratory uniquely combines several model organisms, namely the fly Drosophila melanogaster, the beetle Tribolium castaneum, and the linden bug Pyrrhocoris apterus with molecular techniques in cultured cells and in vitro. We utilize the power of reverse genetic approaches (transgenesis, mutagenesis, RNAi), in these insect models to address basic biological questions as well as insect specific issues in the context of intact, developing organisms. The biological processes of our interest include:
Hormonal and genetic regulation of insect development, metamorphosis and oogenesis.
- Molecular action of lipophilic insect hormones; juvenile hormone; nuclear hormone receptors
Insect endocrinology; developmental biology; Drosophila genetics; reverse genetics
of transcription factors in morphogenesis
While juvenile hormone (JH) regulates multiple aspects of insect development, reproduction, and physiology, our current knowledge of the JH signaling pathway is limited to several genes.
Synthetic JHR agonists offer a smart means of controlling insects, but existing juvenoid insecticides harm non-target species. Compounds blocking JH action would make superior insecticides, yet none are available.
Discovery of the bHLH-PAS protein Methoprene-tolerant (Met) as the ligand-binding subunit of an intracellular JH receptor (JHR) has opened avenues to understanding the molecular action of JH in insect biology. Our goal is to harness JHR in order to uncover both: (i) unknown players required for JH signaling during insect development, and (ii) novel compounds for safe and selective endocrine regulation.
Molecular function of the JHR
> Post-translational modification: Using a combination of in-vitro, cell-based, and genetic experiments on Drosophila, we want to know the roles of Met phosphorylation, protein-protein interaction with its partner Taiman, and nuclear import.
> Ligand stereoselectivity: Working with geometric and optical stereoisomers of JH, we have been able to define the key features determining the agonist activity of the natural hormone acting upon the JHR protein.
Novel JHR agonists and antagonists
> Selective JHR agonists: Our automated, high-throughput screening of chemical libraries using cell-based reporters of JHR activities yields novel agonists, some of which display species-specific JH-like effects on insects. We develop these compounds and strive to understand their mode of interaction with the JHR.
> Peptidic juvenoids: Small derivatives of p-aminobenzoic acid present extremely species-selective JH mimics. We have determined the JHR agonist action of these compounds to develop them further.
> Putative JHR antagonists: We apply the above HTS approach to discover JHR antagonists for potential use as research tools and future insecticides.
Unknown genetic components of JH signaling
> Genetic approach: We use RNA-seq in Drosophilamisexpressing or lacking the JHR to uncover hitherto unknown genes regulated by the intracellular JH receptor.
> HTS approach: In parallel, the cell-based reporter assays described above are employed towards RNAi-mediated, high-throughput screening for genes involved in JH signaling.