Frontiers of Science: Profs. Gilles van Wezel and Jacques Neefjes
November 3rd at 12:00
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 (email@example.com)
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 firstname.lastname@example.org
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. Aim is to go beyond the known horizons and provide novel insights into the regulatory pathways that control growth, development and antibiotic production of the actinomycetes, and to understand how cells cooperate and differentiate within multicellular systems. This knowledge finds its application in lead discovery and innovative technologies for growth and screening of industrial producer strains. The research is based on state-of-the-art metabolomics, genomics, chemical ecology and modelling approaches and the most advanced imaging technologies. Ground-breaking discoveries include the discovery of the Lugdunomycins, a novel class of polyketides with unprecedented chemical scaffold, the development of elicitors that activate antibiotic production, and the SsgA-like proteins, which recruit FtsZ to division sites during sporulation. 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 centred on three major themes that connect to various NWA agenda points:
1. Antigen presentation by Class I and II MHC: MHC molecules are fundamental mediators of adaptive immunity, where class I MHC governs recognition of virus-infected and tumor cells by the immune system, while class II MHC instigates anti-bacterial responses and helps CTL activation. In this arena, Neefjes’ work has focused around the main theme of how MHC molecules acquire and display antigenic peptides to allow anti-viral and anti-tumor immune responses.
2. Bacterial infections and cancer: Neefjes expanded his work on endosomes to the phagosome, where various pathogenic bacteria proliferate inside the host. Upon fusion of phagosomes with lysosomes, bacteria become degraded and presented to the immune system. Neefjes showed that bacteria, such as Salmonella and M. tuberculosis, activate host kinase AKT1, which prevents fusion and bacterial destruction.
3. Anthracyclines and the efficacy/side-effect puzzle: 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. This ‘dogma’ failed to explain dramatic variation in clinical outcomes between structurally different anthracyclines. In a breakthrough study, Neefjes showed that some anthracyclines, can also generate chromatin damage by ejecting histones from DNA.
Blin K., Shaw S., Kloosterman A.M., Charlop-Powers Z., Wezel G.P. van, Medema M.H. & Tilmann W. (2021), antiSMASH 6.0: improving cluster detection and comparison capabilities, Nucleic Acids Research 49(W1): W29-W35.
Bergeijk D.A. van, Terlouw B.R., Medema M.H. & Wezel G.P. van (2020), Ecology and genomics of actinobacteria: new concepts for natural product discovery, Nature Reviews Microbiology 18(10): 546-558.
Carrión V.J., Perez-Jaramillo J., Cordovez V., …; Oost J. van der, Paulson J.N., Mendes R., Wezel G.P. van, Medema M.H. & Raaijmakers J.M. (2019), Pathogen-induced activation of disease-suppressive functions in the endophytic root microbiome, Science 366(6465): 606-612.
Jongsma, M.L.M.; Waard, A.A. de; Raaben, M.; Zhang, T.; Cabukusta, …; Neefjes, J. & Spaapen, R.M. (2021), The SPPL3-defined glycosphingolipid repertoire orchestrates HLA class I-mediated immune responses, Immunity 54(1): 132-+.
Boomen, D.J.H. van den; Sienkiewicz, A.; Berlin, I.; Jongsma, M.L.M.; Elsland, D.M. van; Luzio, J.P.; Neefjes, J.J.C. & Lehner, P.J. (2020), A trimeric Rab7 GEF controls NPC1-dependent lysosomal cholesterol export, Nature Communications 11(1)
Qiao X., Zanden S.Y. van der, Wander D.P.A., …; Mummery C.L., Smit L., Arens R., Li J., Overkleeft H.S. & Neefjes J.J.C. (2020), Uncoupling DNA damage from chromatin damage to detoxify doxorubicin, Proceedings of the National Academy of Sciences of the United States of America 117(26): 15182-15192.
- 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.