Olsen Lab

With a foundation in chemical synthesis the Olsen Lab is developing peptidomimetic secondary structures and using naturally occurring macrocyclic peptides for development of HDAC inhibitors and quorum sensing modulators. We are also developing a suite of chemical tools for investigation of the function of human lysine deacylase enzymes

Laboratory

 

News 2021
January, 
Julie and Alexander presented their impressive PhD works at the DRA Winter School.
Drug Research Academy Winter School 2021 - Olsen Lab PhD students

January, Two papers accepted in RSC Chem Biol. Congratulations to first authors Alexander and Kathrin on their great efforts in developing SIRT2 and SIRT3 inhibitors, respectively.

January, Carlos's microarray work is published in Nature Communications link. See also a Behind the Paper post and a press release from the UCPH_Health.

News 2020
December, New graduate student Peter H. G. Egelund joins the lab to do a joint PhD with Novo Nordisk A/S.

October, Welcome to three new PhD students in the lab. Daniela, Benjamin, and Tobias. We look very much forward to working with you.

September
, We are happy to welcome James, Javier, and Athanasios who will perform their MSC thesis work in the lab.

September
, Congratulations to Sam and Michaela who both defended their MSc thesis and were awarded the best grade in the scale.

July,
Bengt receives this year’s prize for the best PhD theses in organic chemistry awarded by the Section for Organic Chemistry, Danish Chemical Society. Huge congratulations. Very well deserved!

June, Congratulations to Isabelle on the successful defense of her PhD theses via Zoom.

May, Congratulations to Michael on the successful defense of his PhD theses via Zoom.

May, We are grateful to the Independent Research Fund Denmark for supporting 3 different projects in the lab. We now look forward to recruiting 3 new graduate students to work on bioisosteres to target human SIRT5, PROTAC degraders that target HDACs, and autoinducing peptides from staphylococci.

logo Independent Research Fund Denmark


February, CAO attends the Peptides GRC

January, We thank the Carlsberg Foundation for funding equipment to start doing electrochemistry in the lab. Kudos to Bengt for writing this proposal!

logo Carlsbergfondet

News 2019
December, We are happy to share work from Nima and Alexander on "Considerations for Drug Design using Mechanism-based Sirtuin Inhibition" via ChemRxiv 2019,  

December, We are currently looking for two ambitious and talented postdocs to work on our ERC-funded project on chemical tools to investigate post-translational modifications. For more information and on-line application, please see HERE.

November, We can finally report on our new design strategy for activity-based probes to investigate lysine acylation. Available at ChemRxiv 2019,. Congratulations on the massive achievement Michael et al.

November, CAO visits the chemistry department at TU Munich for a great day of interaction with faculty and giving a seminar.

September, Nima presents his project to the Hørslev Foundation. Once again, thank you for this great effort Nima.

Nima presents his project to the Hørslev Foundation

September, Check out the write-up in Dansk Kemi (in Danish...) of Bengt's protocol for AIP identification. Also featured on the cover.

logo Dansk Kemi

August, Congratulations to Nikos who successfully defended his MSc thesis on 13C-labeled HDAC inhibitors for NMR studies.

July, We say goodbye to Jiyan and Simona who have defended their MSc theses and will go on to pursue PhD studies with David Spring (Cambridge) and Ryan Shenvi (Scripps), respectively. Well done guys.

July, We thank the Hørslev Foundation for supporting the lab with an equipment grant. Kudos to Nima for securing this!

logo Hørslev fonden

July, Congratulations to Bengt for successfully defending his PhD. I am happy that you have decided to stay in the lab for another 2 years.

July, We hosted a DRA symposium, featuring Phil Dawson, Thomas B. Poulsen, and Kristian Strømgaard as the speakers.

June, We are happy to announce that the LEO foundation has generously supported our work on quorum sensing through their Open Competition Grant program.

logo leo-fonden

June, Congratulations to Alexander for securing a Fulbright Scholarship to support his sabbatical at Scripps Research, La Jolla, CA in the lab of Prof. Kim Janda.

logo Fulbright

June, Congratulations to Carlos for successfully defending his PhD. I am happy that you have decided to stay in the lab for while still.

May, Check out the press release from the UCPH on our work on identifying new staphylococcal AIPs here.

April, Big congratulations to Bengt on his Nature Chemistry paper now being on-line. Thanks for the nice News & Views write-up as well.

January, Pablo's Minireview on arylfluorosulfate-based probes is now available at Angewandte Chemie.

News 2018
November, Congratulations to Simona for securing a Novo Scholarship to support her during her MSc thesis work. Well done!

logo novozymes

November, Thanks to the Carlsberg Foundation for granting us funding for a cell imager system.

logo Carlsbergfondet

November, Welcome to Patricia who is joining us as an intern to work on photo cross-linking probes

October, We gratefully acknowledge the Lundbeck Foundation for generously providing a grant to support running costs and new equipment.

September, We welcome Ahmed to the lab, who is joining us as a postdoctoral fellow from the Meldal laboratory.

August, Bengt wins 1st prize at the DRA Summer School for his lecture on synthesis, SAR, and identification of auto-inducing peptides. Well done!!

August, Our work on HDAC11 was highlighted by UCPH Health Science News as well as BioWorld Science and BCN News.

August, We welcome Adela and Anja who are joining us from KIT in Karlsruhe and Albert-Ludwigs University in Freiburg, respectively to perform their MSc theses.

June, Congratulations to Nima for claiming runner-up spot at the Danish EFMC YI prize symposium.

June, We are looking for a talented and ambitious candidate for a postdoctoral position. For more details and to apply, please go to: link

May, New article on HDAC11 in Cell Chem. Biol. Well done and congrats Iacopo, Carlos, and Andreas.

April, We welcome Jiyan and Nikos who are joining us to perform their MSc theses.

April, Welcome to Dr. Martin Roatsch who is joining us as a postdoctoral fellow funded by the German Science Foundation (DFG).

dgf deutsche forschungsgemeinschaft

March, We welcome PhD student Julie E. Bolding and laboratory technician Katrine J. Krydsfeldt to the laboratory.

February, Congratulations Rita on earning your PhD degree.

February, We are looking for a student assistant to help with financial issues. Please see, link.

January, Andreas just submitted our latest results on characterization of a sirtun depropionylase from Lactobacillus acidophilus NCFM. Read the manuscript at bioRxiv.

January, Iacopo and Nima both successfully defended their PhD theses. Congratulations!

News 2017
December, We are thankful to the Novo Nordisk Foundation for a new grant supporting work towards chemically modified histones.

logo Novo Nordisk

November, We are seeking a talented and motivated candidate for a PhD position aiming to investigate sirtuin enzymes using chemical tools. For more information, please click here.
November, We just used the preprint option for the first time. Read about our latest findings on HDAC11 at bioRxiv.
November, We welcome Simona Kotesová to the lab. Simona is joining us from UC Berkeley to be a lab assistant.
September, We welcome Alexander L. Nielsen to the lab. Alexander is joining us to perform his PhD studies.
August, Welcome to Pablo Martin-Gago who is joining us as assistant professor from a postdoctoral position at the Max Planck Institute in Dortmund.
May, Carlos has been selected for a talk at this year's High Throughput Chemistry and Chemical Biology Gordon Research Seminar, Congratulations!
April, We are looking for highly motivated and ambitious postdocs. To read more about the project and apply, please see: announcement
March, We are looking for a highly motivated and ambitious PhD student. To read more about the project and apply, please see: PhD-MedChem
February, We welcome Pieter Moyson from Vrije Universiteit Brussel in Belgium, who will join the lab as an Erasmus student.
February, We welcome Kathrin Troelsen to the lab. Kathrin is joining us from DTU to perform her PhD studies.
January, We welcome Isabelle Wellhöfer to the lab. Isabelle is joining us from Karlsruher Institut für Technologie (KIT) to perform her PhD studies.

News 2016
November, We thank the ERC for the award of a Consolidator Grant to CAO.

logo erc

November, We welcome Alessia Lucidi to the lab, who is joining us on exchange from the University of Rome.
November, We welcome Michael Bæk and Marina Auth to the lab. Michael is joining us to perform his PhD studies, and Marina is an exchange student from the University of Freiburg.
September, We welcome Huy and Jiyan who will be performing their one-year scholar projects in the lab.
August, Congratulations to Iacopo on winning best poster award at the DRA Summer School.
July, Congratulations to Alex and Andreas on publication of their paper as a Featured Article in Cell Chem. Biol.
July, We are looking for two highly motivated and ambitious PhD students. To read more about the projects and apply, please see: PhD-ChemBiol and PhD-Bioorg
June, We are grateful to the Danish Independent Research Councils, FTP and FNU, for supporting our lab.
April, Big congratulations to Betül on a very successful defense of her PhD thesis Monday 25th of April.
April, Andreas, Helle, Iacopo, Nima, Ragnhild, and CAO attended the FRIAS 3rd Freiburg Epigenetic Spring Meeting.
April, We welcome Carlos Moreno-Yruela to the lab. Carlos is joining us to perform his PhD studies.
March, Check out our News & Views piece in Nat. Chem. Biol. as well as Mazitschek's original research article.
March, Congratulations to Andreas on his two first author publications in jbc and MedChemComm, respectively.
March, We welcome Martin Fontenas to the lab. Martin is joining us as an intern from Université de Montpellier.
February, CAO attended the Gordon Conference on Peptides in Ventura, CA, and was discussion leader for one of the sessions.
February, We welcome Alex Maolanon to the lab. Alex is joining us as a postdoctoral fellow.
February, Congratulations to Iacopo on his first publication, which is on sirtuin substrates and is appearing in J. Med. Chem.

News 2015
December, We thank the Novo Nordisk Foundation and the Carlsberg Foundation for supporting our research in the fall's call for proposals.
November, CAO visited the University of Geneva to meet with faculty and give a lecture on HDAC and sirtuin work from the lab.
November, We are currently looking for a talented and motivated PhD student. The deadline is 30 November, 2015. For the full posting and to apply, please see https://employment.ku.dk/phd/?show=781825.
October, We welcome Bengt Gless to the lab. Bengt is joining us from Germany to perform his graduate studies.
August, Check out the write-up on our two recent publications on foldamers here.
August, We welcome Ragnhild Ohm to the lab. Ragnhild is joining us as a postdoctoral fellow.
August, CAO gives a lecture on foldamers at the 9th Peptoid Summit in Berkeley.
July, Congratulations to Jonas and Jens on the acceptance of their Accounts of Chemical Research article.
July, Congratulations to Jens et al. on the cover of JOC. For details see here.
June, We are currently looking for a talented and motivated PhD student. The deadline is 30 June, 2015. For the full posting and to apply, please see https://employment.ku.dk/phd/?show=745951.
May, Jonas's work on a new beta-peptoid foldamer was published in Nature Communications. Congratulations!
May, We welcome Julie L. H. Madsen to the lab. Julie is joining us as a postdoctoral fellow.
April, CAO presented a poster at this year's 50th edition of the Bürgenstock Conference.
April, Jens successfully defended his PhD Thesis. Congratulations!
March, Also congratulations to Jens and Kathrine et al. on the selection of their paper for the Cover of JOC.
February, Congratulations to Jens and Kathrine et al. on the acceptance of their Full Article in JOC.
January, We welcome Andreas M. Christiansen who will perform his M.Sc. thesis work in the lab.

News 2014
November: We welcome Iacopo Galleano who will join the group from Italy to perform his graduate studies.
November: CAO laboratory finally moves in to the newly renovated facilities at Universitetsparken, Copenhagen.
October: Congratulations to Alex and Jesper et al. on the recent paper on macrocyclic HDAC inhibitors in J. Med. Chem., and thanks to all our collaborators involved.
September: Betül, Helle, and Jens helped co-organize a very successful TOKS meeting at DTU.
September: CAO gave his inaugural lecture on 19/9-2014.
September: CAO received the EFMC Prize for a Young Medicinal Chemist in Academia at the EFMC-ISMC in Lisbon, Portugal.
August: Helle, Betül, and Jonas all gave oral presentations at the ACS meeting in San Francisco. Well done all of you!
August: Congratulations to Jesper, Betül, Kathrine, and Andreas on the acceptance of their work in the MedChemComm Special Issue on Epigenetics.
July: CAO participated in the Gordon Conference on ‘Enzymes, Co-Enzymes, and Metabolic Pathways’.
June: CAO lectures at a Danish Chemical Society Symposium on Recent Advances in Foldamers Research.
June: Congratulations to Betül and Jonas on the acceptance of their work in the Tetrahedron Special Issue on Peptide Macrocycles and BBA Biomembranes, respectively.
June: We welcome Nima Rajabi (graduate student) and Kathrine Wich (research assistant) to the group.
May: Andreas and CAO were co-organizers of the 3-day event: Posttranslational Protein Modifications in Epigenetics and Metabolism, Copenhagen 26-28 May.
May: Welcome back to Jens, who returns to the lab after a six-month stay in Prof. Kirshenbaum’s laboratory at NYU.
April: A large cross-institutional study with enzyme kinetic contributions from our laboratory was published in Cell Metabolism. Congratulations Andreas.
March: CAO gave a lecture on beta-peptoids at the ACS National Meeting in Dallas.
March: Both Alex and Jonas defended their Ph.D. theses. Congratulations!
March: The Olsen Laboratory moves to the ‘Center for Biopharmaceuticals’ at University of Copenhagen, where CAO will assume the position of professor and principal investigator.
February: Work from Andreas, Helle, and Gyrithe was published in a special issue of ChemMedChem and was chosen for the Back Cover illustration. Congratulations on a very nice piece of work.
February: Christian Andersen and Mohammad Daoud defended their B.Sc. theses. Congratulations!
January: The group participates in the Torkil Holm Visions in Chemistry Symposium.
January: Jesper defended his Ph.D. thesis on January 23th, and is leaving academia for a job at Zealand Pharma. Congratulations!

News 2013
December: We gratefully acknowledge the Carlsberg Foundation for funding a microwave peptide synthesizer.
September: CAO gave a lecture at the 10th Australian Peptide Conference in Penang, Malaysia.
September: Christian Andersen and Mohammad Daoud joined the group to perform their B.Sc. thesis work on acyllysine substrates.
August: Helle, Andreas, and CAO attended the FASEB Conference on HDACs and Sirtuins in Barga, Lucca, Italy.
July: Congratulations to Jesper, Helle, and Alex on the acceptance of their azumamide work for publication in J. Med. Chem.

July: Congratulations to Emma for receiving the top grade for her B.Sc. thesis.

June: Andreas attended the Gordon Conferences on Bioorganic Chemistry and High-Throughput Chemistry & Chemical Biology.

June: CAO attended the American Peptide Symposium.

April: Jonas and Jens presented posters at the Foldamer Symposium in Paris.

April: Betül and Helle presented posters at the TOKS Meeting in Odense, DK.

April: CAO gave a lecture at the ACS National Meeting in New Orleans.
March: CAO gave a lecture at the PepCon conference in Suzhou, China. 

January: Congratulations to Jonas on the acceptance of his peptoid rotamer study for publication in JACS. 

January: Congratulations to Andreas upon his award of a Sapere Aude postdoc grant. 

January: We welcome Saswati Chakladar who will join the group as a postdoctoral fellow.

News 2012
December: Villumfonden is gratefully acknowledged for a ”blokstipend” grant.
October: CAO gave a lecture at University of Barcelona.

July: Congratulations to Andreas on the acceptance of his work on KDAC substrates in Angewandte Chemie.

June: CAO gave a lecture at the Danish Chemical Society Annual Meeting in Odense, DK. 

May: Andreas’s work on sirtuin substrates was accepted for publication in J. Med. Chem. Congratulations! 

May: CAO participated in this years Bürgenstock Conference and TIDES-2012.

March: We welcome Betül Kitir who joins the group to perform her M.Sc. thesis work.

January: CAO receives a JSP fellowship from the organizing committee of the Bürgenstock Conference.

News 2011
December: We gratefully acknowledge the Carlsberg Foundation for funding a plate reader.

November: Congratulations to Jesper for winning the Pharma Student Award 2011 at University of Copenhagen for his master thesis work.

November: We welcome Jens Engel-Andreasen who will join the group to perform his graduate studies.

November: CAO participates in the DR2 television program "Danskernes Akademi" for a themed series in recognition of the International Year of Chemistry.

July: Collaborative work from the laboratories of Prof. Ghadiri and Prof. Balch at The Scripps Research Institute was accepted for publication in ACS Med. Chem. Lett.

July: CAO participates in the EuCheMS Organic Division Young Investigator Workshop, followed by ESOC 2011.

June: CAO participates in the American Peptide Symposium in San Diego.

News 2010
December: Jesper Villadsen (graduate student) and Andreas S. Madsen (postdoctoral fellow) join the group.

December: CAO gives a lecture in the Frontiers in Peptide Chemistry Symposium at Pacifichem. 

November: Jonas Striegler Laursen and Alex Maolanon join the group to perform their graduate studies.

October: CAO participates in the talk show Lounge on TV2 Lorry.

October: CAO receives a Lundbeck Foundation Junior Group Leader Fellowship ($1.75 mil.).

June: CAO receives a Steno grant from the Danish Council for Independent Research/Natural Sciences.

 

 

 

 

 

Research projects

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ε-N-Acyllysines are prevalent, reversible posttranslational modifications involved in a wide range of biological processes within all domains of life. We apply various chemical techniques to interrogate enzymes that recognize and/or reverse posttranslationally acylated lysine residues.

Substrate screening. We develop chemically modified peptides for the discovery and elucidation of unprecedented enzymatic activities of lysine deacylases (KDACs). To this end, we exploit in vitro high-throughput fluorogenic assays and complementary LCMS-based assays.

Affinity-based probes. We develop novel affinity-based probes (ABPs) for investigating enzymes that recognize or cleave posttranslationally modified lysine residues. These probes utilize a photo-crosslinking group to trap the enzymes by a covalent bond. This approach allows us to investigate enzymatic readers and erasers of posttranslational lysine modifications.

SPOT array profiling. Taking advantage of microarray technologies, we aim to elucidate the native behavior of histone deacetylase-containing complexes. We prepare CelluSPOT peptide microarrays including non-canonical and modified amino acids, which provide information on substrate recognition in a high-throughput manner.
Olsen Lab, Peptide microarrays ans HDAC inhibitors, Nature Communications 2021

Inhibitors of the zinc-dependent HDACs. Posttranslational modifications of histone proteins play key roles in regulating transcription. HDACs are among the enzymes that contribute to the highly dynamic and diverse decoration of histone protein side chains. HDAC inhibitors are in the clinic for treatment of various hematological cancers. However, it remains challenging to dissect the importance of individual isozyme activity. We are currently working towards subtype-selective inhibitors. These compound will be valuable tools to investigate the biological consequences of temporal inhibition of individual HDACs.

Sirtuin inhibitors. The sirtuin enzymes are involved in a variety of biochemical contexts and may therefore be potential therapeutic targets through either activation or inhibition by small molecules. Using both solution- and solid-phase peptide synthesis, we strive to develop potent and selective inhibitors of the sirtuin enzyme family. By taking advantage of both structural and mechanistic insight, we develop mechanism-based inhibitors to address sirtuin function.

Representative publications:
C. Moreno-Yruela, C. A. Olsen. Efficient Fluorogenic Assays for Histone Deacetylases: Screening and Determination of Kinetic Parameters. STAR Protoc2021, 2, 100313.

C. Moreno-Yruela, M. Bæk, A.-E. Vrsanova, C. Schulte, H. M. Maric, C. A. Olsen. Hydroxamic Acid-Modified Peptide Microarrays for Profiling Isozyme-Selective Interactions and Inhibition of Histone Deacetylases. Nat. Commun. 2021, 12, 62 (ChemRxiv 2020, DOI: 10.26434/chemrxiv.11513163.v2).

M. Bæk, P. Martín-Gago, J. S. Laursen, J. L. H. Madsen, S. Chakladar, C. A. Olsen. Activity-dependent Probes Containing epsilon-N-Thioacyllysine and epsilon-N-Acyl-(delta-aza)lysine Residues. Chem.–Eur. J. 2020, 26, 3862–3869 (ChemRxiv 2019, DOI: 10.26434/chemrxiv.10315502).

C. Moreno-Yruela, I. Galleano, A. S. Madsen, C. A. Olsen. Histone Deacetylase 11 is an ε-N-Myristoyllysine Hydrolase. Cell Chem. Biol. 201825, 849–856.

N. Rajabi, M. Auth, K. R. Troelsen, M. Pannek, D. P. Bhatt, M. Fontenas, M. D. Hirschey, C. Steegborn, A. S. Madsen, C. A. Olsen. Mechanism-based Inhibitors of the Human Sirtuin 5 Deacylase: Structure–Activity Relationship, Biostructural, and Kinetic Insight. Angew. Chem. Int. Ed. 2017, 56, 14836–14841.

B. Kitir, A. R. Maolanon, R. G. Ohm, A. R. Colaço, P. Fristrup, A. S. Madsen, C. A. Olsen. Chemical Editing of Macrocyclic Natural Products and Kinetic Profiling Reveal Slow, Tight-Binding HDAC Inhibitors with Picomolar Affinities. Biochemistry 2017, 56, 5134–5146.

A. R. Maolanon, A. S. Madsen, C. A. Olsen. Innovative Strategies for Selective Inhibition of Histone Deacetylases. Cell Chem. Biol. 2016, 23, 759–768.

C. A. Olsen. Expansion of the Lysine Acylation Landscape. Angew. Chem. Int. Ed. 2012, 51, 3755–3756.

 

 

 

 

 

 

 

 

 

We are interested in the development of methods for chemical peptide synthesis, cyclization, and site-selective modification to furnish bioactive chemotypes. One problem that we are currently investigating is the cross-talk between bacterial pathogens through the quorum sensing (QS) system. In these studies we aim to increase the understanding of co-colonization and to identify new anti-virulence compounds in collaboration with Prof. Hanne Ingmer and SSI. 

Peptide cyclization methodology. We focus on the development of efficient strategies for synthesis of cyclic peptides based on chemoselective cyclization. Our aim is to minimize protecting group manipulations, to simplify the purification, and to speed up the workflow to achieve the final peptides.

QS inhibitors. The communication of Staphylococci is based on secreted autoinducing peptides (AIPs), which are detected by the cognate QS system and activate the system when sufficiently high concentrations are present. The activation leads to the production of virulence factors and an increased expression of the QS components. This population density controlled auto-feedback loop is responsible for the virulence of an infection. The inhibition of the QS circuit has been shown to attenuate infections and represents an alternative approach in dealing with multi-resistant bacteria. We are interested in identifying new AIP-based inhibitors and other naturally occurring QS inhibitors, like the solonamides, as well as to investigate their structure–activity relationships enabled by chemical synthesis.

Representative publications
B. H. Gless, M. S. Bojer, P. Peng, M. Baldry, H. Ingmer, C. A. Olsen. Identification of Autoinducing Thiodepsipeptides from Staphylococci Enabled by Native Chemical LigationNat. Chem. 201911, 463–469.

B. H. Gless, C. A. Olsen. Direct Peptide Cyclization and One-Pot Modification Using the MeDbz Linker. J. Org. Chem. 2018, 83, 10525–10534.

B. H. Gless, P. Peng, K. D. Pedersen, C. H. Gotfredsen, H. Ingmer, C. A. Olsen. Structure–Activity Relationship Study Based on Auto-Inducing Peptide (AIP) from Dog Pathogen S. schleiferi. Org. Lett. 2017, 19, 5276–5279.

J. Canovas, M. Baldry, M. S. Bojer, P. S. Andersen, B. H. Gless, P. K. Grzeskowiak, M. Stegger, P. Damborg, C. A. Olsen, H. Ingmer. Cross-talk Between Staphylococcus aureus and other Staphylococcal Species via the agr Quorum Sensing System. Front. Microbiol. 2016, 7, 1733. [Corrections: 2017, 8, 1075 and 20178, 1949]

B. Kitir, M. Baldry, H. Ingmer, C. A. Olsen. Total Synthesis and Structural Validation of Cyclodepsipeptides Solonamide A and B. Tetrahedron 2014, 70, 7721–7732.