Institute of Organic Chemistry and Biochemistry of the CAS

Granting Departments:	Department of Chemistry of Natural Compounds Institute of Organic Chemistry and Biochemistry of the CAS
Study Programme/Specialization:	Biochemistry and Bioorganic Chemistry ( in English language )
Supervisor:	Dr. habil. Ullrich Jahn

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The axinellamines belong to the most complex alkaloids with interesting biological properties. With this project biomimetic approaches will be explored to enable short total syntheses of the natural products themselves and of analogs. Their biological profile will be investigated in collaboration.

Granting Departments:	Department of Biochemistry and Microbiology Institute of Organic Chemistry and Biochemistry of the CAS
Study Programme/Specialization:	Biochemistry and Bioorganic Chemistry ( in English language )
Supervisor:	Mgr. Tomáš Kouba, Ph.D.

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Effective treatment against influenza viruses (Flu) suffers from virus resistance. Therefore, there is a great demand for exploring new drug targets and developing effective novel antivirals. This is challenging, since there is only a limited number of antiviral targets for rational drug design. This project will tackle both; it will explore and verify a new target and develop inhibitors against it. Cutting edge results in structural biology of the influenza RNA-dependent RNA polymerase (FluPol), identified a common general mechanism of Flu RNA transcription and replication cycle. The mechanism is entirely dependent on binding of viral endogenous RNA molecules to specific sites on the FluPol. Aided by already existing cryo-EM structures of FluPol, we will design inhibitors based on the sequence, atomic structure and interactions with the protein, and add extensive chemical modification to these viral RNAs. We will then test whether they can inhibit FluPol by in vitro and in cell-based experiments. Targeting these RNA binding sites and using RNA-scaffold based molecules is an innovative concept and expected to be robust in respect to the development of viral resistance. Altogether, the approach has great potential to bring a new universal paradigm to the field of antiviral drug discovery.

Granting Departments:	Department of Chemistry of Natural Compounds Institute of Organic Chemistry and Biochemistry of the CAS
Study Programme/Specialization:	Biochemistry and Bioorganic Chemistry ( in English language )
Supervisor:	Mgr. Radim Nencka, Ph.D.

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The Ph.D. student will design and synthesise novel methyltransferase (MTase) inhibitors targeting viral, fungal or human MTases. The student will use in silico approach to speed up the development of potential drugs, but the main part of the assignment will be the organic synthesis. Preparation of suitable ligands bearing a fluorescent tag will enable the efficient development of a screening assay.

Granting Departments:	Department of Chemistry of Natural Compounds Institute of Organic Chemistry and Biochemistry of the CAS
Study Programme/Specialization:	Biochemistry and Bioorganic Chemistry ( in English language )
Supervisor:	Mgr. Tomáš Pluskal, Ph.D.

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Our lab combines cutting-edge experimental (e.g., LC-MS, metabolomics, RNA-seq) and computational (e.g., bioinformatics, molecular networking, machine learning) approaches to develop new workflows for the discovery and utilization of bioactive molecules derived from plants. This project will focus on screening many plant species using liquid chromatography mass spectrometry to discover and isolate unique chemicals (metabolites), including basic characterization of their bioactive potential.

Granting Departments:	Department of Biochemistry and Microbiology Institute of Organic Chemistry and Biochemistry of the CAS
Study Programme/Specialization:	Biochemistry and Bioorganic Chemistry ( in English language )
Supervisor:	prof. Ing. Michal Hocek, DSc.

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Nucleotides bearing specific ligands or reactive groups will be designed and synthesized, from which modified DNA will be synthesized by enzyme methods and used to attach target proteins. Applications will include multi-enzyme systems.

Granting Departments:	Department of Biochemistry and Microbiology Institute of Organic Chemistry and Biochemistry of the CAS
Study Programme/Specialization:	Biochemistry and Bioorganic Chemistry ( in English language )
Supervisor:	prof. Ing. Michal Hocek, DSc.

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Modified 2'-deoxyribonucleoside-triphosphates will be synthesized and used in enzymatic synthesis of oligodeoxyribonucleotides and DNA bearing several modifications at specific positions using a novel approach involving repeated annealing of RNA templates, primer extension and RNA digestion. Applications will include the spatially defined attachment of several different biomolecules, particularly proteins, to DNA.

Granting Departments:	Department of Biochemistry and Microbiology Institute of Organic Chemistry and Biochemistry of the CAS
Study Programme/Specialization:	Biochemistry and Bioorganic Chemistry ( in English language )
Supervisor:	Ing. Iva Pichová, CSc.

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Terpenoid secondary metabolites are used by organisms for communication and defense, and their biological activities are exploited by industries such as pharmaceuticals, cosmetics, or food and flavour. This PhD project addresses the question of evolutionary origin of terpenoid biosynthesis in insects. Terpene synthases (TPS) are key enzymes responsible for the conversion of prenyl pyrophosphates into terpenes, and insect TPSs are unrelated to their plant or microbial counterparts. They have evolved multiple times independently in different insect lineages. Our understanding remains limited in terms of their reaction mechanisms and structure-activity relationships. Within this PhD project, the doctoral candidate will functionally characterize a set of insect terpene synthases from unrelated insect clades and define their common and idiosyncratic structural features acquired during their multiple independent origins. This PhD project is funded by the European MSCA Doctoral Network ‘ModBioTerp’ and the grant support for the broader research project is funded by Ministry of Education, Youth, and Sports (2024-2027).

Granting Departments:	Department of Chemistry of Natural Compounds Institute of Organic Chemistry and Biochemistry of the CAS
Study Programme/Specialization:	Biochemistry and Bioorganic Chemistry ( in English language )
Supervisor:	Dr. habil. Ullrich Jahn

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We just accomplished approaches to glycine alkoxyamines, which hold large promise in bioconjugation. With this project the potential of these non-natural amino acid derivatives for approaching new peptide architectures will be explored.

Granting Departments:	Department of Chemistry of Natural Compounds Institute of Organic Chemistry and Biochemistry of the CAS
Study Programme/Specialization:	Biochemistry and Bioorganic Chemistry ( in English language )
Supervisor:	Mgr. Radim Nencka, Ph.D.

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The PhD student will focus on the design and organic synthesis of new methyltransferase inhibitors, whether derived from viral, fungal, or human sources. In the course of developing these compounds, the candidate will employ in silico molecular modeling to streamline and accelerate the search and optimization of inhibitors. Nonetheless, the main emphasis of the project will remain on the organic synthesis of potential therapeutic agents. Additionally, the project will include the preparation of ligand analogs equipped with suitable tags, whether fluorescent or functional (e.g., biotin for pull-down assays, thalidomide for PROTAC technology).

Granting Departments:	Department of Chemistry of Natural Compounds Institute of Organic Chemistry and Biochemistry of the CAS
Study Programme/Specialization:	Biochemistry and Bioorganic Chemistry ( in English language )
Supervisor:	Mgr. Tomáš Pluskal, Ph.D.

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Our lab combines cutting-edge experimental (e.g., LC-MS, metabolomics, RNA-seq) and computational (e.g., bioinformatics, molecular networking, machine learning) approaches to develop new workflows for the discovery and utilization of bioactive molecules derived from plants. The aim of this project will be to engineer new microbial platforms for the bioproduction of terpenoid precursors and terpenoids derived from them.

Granting Departments:	Department of Biochemistry and Microbiology Institute of Organic Chemistry and Biochemistry of the CAS
Study Programme/Specialization:	Biochemistry and Bioorganic Chemistry ( in English language )
Supervisor:	David Marcelo Sabatini, M.D., Ph.D.

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My lab has a long-standing interest in the regulation of growth and metabolism. This interest stems from our early work on the pathway anchored by mTOR protein kinase, which we now appreciate is a major regulator of growth and anabolism responds to nutrients. Because we found that lysosomes play a key role in the activation of mTORC1 by nutrients, we began to study lysosomes as well as other organelles, like mitochondria. We developed methods for the rapid isolation and profiling of these organelles (e.g., Lyso-IP), and used them to deorphan the functions of disease-associated genes. Because mTORC1 senses nutrients, we also became interested in the metabolic pathways that cells to use incorporate biomass and generate energy. (1) Nutrient sensing by mTORC1 in vitro and in vivo. We seek to identify the glucose sensor for the mTORC1 pathway; discover nutrient sensors in animals beyond mammals; understand how the nutrient sensors function in vivo. (2) Lysosomes in normal physiology and disease.We seek to understand how common and rare neurodegenerative diseases impact lysosomal function and identify the contents of lysosomes in specialized cells. (3) In collaboration with chemists, we will develop drug-like molecules that target mTOR pathway components as well lysosomal proteins.

Granting Departments:	Department of Chemistry of Natural Compounds Institute of Organic Chemistry and Biochemistry of the CAS
Study Programme/Specialization:	Biochemistry and Bioorganic Chemistry ( in English language )
Supervisor:	Dr. habil. Ullrich Jahn

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With the project, synthetic approaches to complex indoloterpene and their analogs displaying wide-ranging biological activity will be developed.