News

• January 2024: Marek, Lenka, and our collaborators David Sedlak, Roman Tuma et al. posted an original preprint "Unique and Common Agonists Activate the Insect Juvenile Hormone Receptor and the Human AHR" in bioRxiv https://doi.org/10.1101/2024.01.03.574093
• December 2023: Marek is listed among the top 2% best cited authors in 2022 worldwide 
• November 2023: Together with our collaborator, David Sedlak, Marek co-founded a startup company Preagon Biotech to develop precision insecticides based on species-selective JH receptor agonists 
• November 2023: Marek and our collaborator Tomas Dolezal are awarded a joint 3-year GACR grant to study the effect of JH signaling on cellular innate immunity of Drosophila 
• November 2023: We publish an extensive invited review article examining the phylogeny and comparing roles of all bHLH-PAS proteins between insects and vertebrates, in J Mol Biol  https://doi.org/10.1016/j.jmb.2023.168332
• October 2023: Tereza Dolejskova joins our team for her Ph.D. project focused on the role of JH in innate immunity.  
• September 2023: Matej wins the Josef Hlavka Endowment Prize for best students - Congratulations!!!
  
• January 2023: Sarka designs a cell-based system revealing Ligand-dependent interactions of the JH receptor protein Met with Taiman and Hsp90 in real time, in FEBS J. https://doi.org/10.1111/febs.16719
• November 2022: We publish an article Unique peptidic agonists of a juvenile hormone receptor with species-specific effects on insect development and reproduction in collaboration with our colleagues led by David Sedlak (IMG Prague) and Pavel Majer (IOCB Prague) in PNAS with a cover image https://doi.org/10.1073/pnas.2215541119
• July 2022: Sarka, Matej, Marek, and David Sedlak drive to Helsinki to present work at the International Congress of Entomology (https://ice2020helsinki.fi/)
• Summer 2022: Lenka publishes her debut collection of poetry entitled Návraty (Returnings) with the Galén publishing house (Prague) https://www.galen.cz/idistrik/vydav/?PHPSESSID=qh0g4s6uck9map5rmns5741s66&page%5Bbook%5D=6020
• December 2021: Collaboration with our Australian colleagues concluded by publishing on Purification and phosphorylation of JH receptor complexes in J Biol Chem https://doi.org/10.1016/j.jbc.2021.101387
• November 2021: In collaboration with Marcela Nouzova and Fernando Noriega, Marek contributes to an article Epoxidation of juvenile hormone was a key innovation improving insect reproductive fitness in PNAS with a cover image https://doi.org/10.1073/pnas.2109381118
• October 2021: We report de novo synthesis of [3H]JH III and its binding by termite and cockroach JH receptors in Insect Biochem Mol Biol https://doi.org/10.1016/j.ibmb.2021.103671
• June 2021: Matej defends his Master degree cum laude 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: Sarka Tumova joins the team. 
• November 2019: Marek awarded the EXPRO research grant in collaboration with David Sedlák of the CZ-OPENSCREEN national infrastructure for chemical biology. 
• October 2019: Matej Milacek 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 https://doi.org/10.1074/jbc.RA118.005992
• 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

https://onlinelibrary.wiley.com/doi/epdf/10.1111/gtc.12543

Ongoing projects

Rationale

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 Drosophila misexpressing 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.