November 3^rd at 12:00
on-site event
Presidentti auditorium, BioCity
Autumn 2022 poster

Prof. Gilles van Wezel, Leiden University, Netherlands
Ecology-inspired approaches towards antibiotic discovery in Actinobacteria
Prof. Jacques Neefjes, Leiden University Medical Center, Netherlands
Detoxifying anthracycline anti-cancer drugs for new treatment options of relapsed cancer patients
Host: Mikko Metsä-Ketelä (mianme@utu.fi)

Coffee and sandwich served at 11:45

Six students and early-career postdocs are welcome to have a lunch in restaurant Mauno and discuss with Profs. van Wezel and Neefjes after the seminar. This is a great possibility to learn hosting skills in friendly environment and create connections for future. Every student are welcome to join, in spite of which research group they belong to. BioCity Turku will offer the lunch.

If you got interested, please send an email to biocityturku@bioscience.fi

In this double feature of the FoS seminar series, our two speakers present how bioactive natural products can be discovered from microbes and developed into clinical drugs.

The lab of Gilles van Wezel primarily focuses on the actinomycetes, which are multicellular mycelial bacteria that produce two-third of all known antibiotics and many other molecules with medical application. Recent years have seen a resurgence of drug discovery efforts from microbial sources through state-of-the-art metabolomics, genomics, chemical ecology, modelling approaches and advanced imaging technologies. Ground-breaking discoveries include the development of elicitors that activate antibiotic production and the discovery of the lugdunomycins, a novel class of polyketides with unprecedented chemical scaffold. The research of van Wezel is characterized by the strong resonance between fundamental and applied research, and much of his research is supported by public-private partnerships.

Research by Neefjes and his laboratory has centered around several major themes including antigen presentation, bacterial infections and cancer. Relevant for this talk is development of anthracyclines for anticancer chemotherapy. Doxorubicin is a widely used and highly effective anticancer drug, but induces cardiotoxicity that prevents treatment of recurring tumours. When testing chemical modulations of MHC antigen presentation, Neefjes explored one of the most used frequently used classes of anti-cancer drugs—the anthracyclines—which were long thought to act by generating DNA double stranded breaks. In a breakthrough study, Neefjes showed that some anthracyclines, can also generate chromatin damage by ejecting histones from DNA and that the combination of these two activities is the cause of cardiotoxicity. In his recent work he has shown that this allows the development of cardiotoxicity-free anthracyclines for clinical use.

Selected publications

Anthracyclines: biosynthesis, engineering and clinical applications (2022) Mandy B Hulst, Thadee Grocholski, Jacques JC Neefjes, Gilles P van Wezel, Mikko Metsä-Ketelä, Natural Product Reports

Ecology and genomics of Actinobacteria: new concepts for natural product discovery (2020) Doris van Bergeijk, Barbara Terlouw, Marnix Medema, Gilles van Wezel, Nature Reviews Microbiology, 18, 546–558

Omics-based strategies to discover novel classes of RiPP natural products (2021) Alexander M. Kloosterman, Marnix H. Medema, Gilles P. van Wezel, Current Opinion in Biotechnology 69, 60–67

Uncoupling DNA damage from chromatin damage to detoxify doxorubicin (2020) Xiaohang Qiao, et al, Proceedings of the National Academy of Sciences 117, 15182-15192

Drug-induced histone eviction from open chromatin contributes to the chemotherapeutic effects of doxorubicin (2013) Pang et al, Nature Communications 4, 1908

Chemical profiling of the genome with anti-cancer drugs defines target specificities (2015) Pang et al, Nature Chemical Biology, 11, pages 472–480

General information

• You can download all autumn 2022 FoS-seminars as .ics in your calendar from here: https://seafile.utu.fi/d/db29925e6f0e4becb755/
• Registration is not needed for on-site seminars
• Participation list is circulated in the audience
• If you are a student and later wish to get a certificate of attendance from the Frontier of Science seminars, please print out this seminar diary and after the seminar ask the BioCity coordinator to sign it
• Please note that any audio or video recording of the seminars is strictly forbidden.