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Latest ClickGene publications

As the ClickGene project is coming to an end, ClickGene early-stage-researchers (ESRs) continue to disseminate their work through publications in renowned Chemistry journals.

ESRs Nicolo Fantoni, Georgia Menounou and Gianluca Toniolo recently published a paper in Chemistry: A European Journal, which reports a new type of artificial metallo-nuclease for the building of robust inorganic scaffolds.

In November 2018, the work of Gianluca Toniolo (in collaboration with ESRs Maria Louka, Georgia Menounou and Nicolo Fantoni) has been published on the biological reactivity of a novel artificial nuclease. An article of interest for chemotherapeutic activities and published on the American Chemical Society journal ACS Omega.

The Kellett Group in DCU has also recently published two papers in Chem. Soc. Rev and ChemPlusChem. In “Molecular methods for assessment of non-covalent metallodrug–DNA interactions“, the Kellett Group describes a range of molecular methods to explore novel metallodrug-DNA interactions. In “Efficient DNA Condensation by a C3‐Symmetric Codeine Scaffold”, the authors propose a novel nucleic acid condensation agent to be used in gene therapy.

More ClickGene-related publications are foreseen within the next months. You can find the current list of journal articles on the publications page.

ClickGene Final meeting - Dublin City University

On the 6th of December 2018, ClickGene ESRs attended the Final Meeting in Dublin City University (DCU). Organised by the Kellett Group, the final meeting consisted in keynote lectures and ESRs presenting latest advancements in their research projects.

ClickGene PI Dr. Niall Barron from the Irish National Institute for Bioprocessing Research (NIBRT) provided ESRs with insights from the industry by presenting cell engineering approaches to improving biopharmaceutical production in Chinese hamster ovary cells. On the afternoon, Prof. Vickie McKee from DCU gave an overview of X-ray structure analysis.

ClickGene ESR publishes new paper in the Chemistry journal

ClickGene's ESR Ján Matyašovský from IOCB AS CR has recently published a paper in collaboration with Prof Hocek and Dr Pohl of IOCB. The paper contained research results regarding a series of 2-alkylamino-2'-deoxyadenosine triphosphates which was prepared and was found to be substrates for the Therminator DNA polymerase. This enzyme incorporated only one modified nucleotide into the primer. When a template encoding for two consecutive adenines was used, conditions for incorporation of one or two modified nucleotides were found. After the addition of natural dNTPs the enzymatic synthesis led to further extension of the primer resulting in a DNA modified site-specifically in the minor groove. Reactive allylamino- and propargylamino-modified DNA was used for post-synthetic modification using fluorescent labels utilizing click reactions. This approach proved to be useful for the construction of FRET probes for the detection of oligonucleotides.

New ESR publication in Organic Letters

ClickGene’s ESR Alessandro Panattoni from IOCB has recently published, in collaboration with Prof Michal Hocek and Dr Radek Pohl, a new paper on alkyne-linked thymidine nucleotides for faster and more efficient post-synthetic modifications of DNA through CuAAC. Two new building blocks bearing long and flexible linkers between the nucleobase and the terminal alkyne were synthesized and incorporated both chemically and enzymatically into DNA. The flexibility and length of the new linkers resulted in a significant advantage for the reactivity in CuAAC and oligonucleotides bearing these alkyne tethers underwent CuAAC reactions more efficiently than the standard ethynyl- and 1,7-octadiynyl- modified oligonucleotides.

 

New ClickGene ESR work published in Chemical Science

ClickGene’s ESR Sarah Walsh from ATDBio has recently published her first paper in collaboration with Prof Tom Brown and Dr Afaf El-Sagheer. Published in the Chemical Science journal, the work showed how the instability of DNA triplex can be addressed and resolved through the introduction of a thiazole orange (TO) intercalator onto a thymine nucleobase in triplex forming oligonucleotides (TFOs). By overcoming DNA triplexes’ instability, “TOTFO” probes can expand triplex applications into many areas including diagnostics and cell imaging.

New ClickGene Publication in Nucleic Acids Research

The Kellett and Brown groups recently published a collaborative article "Di-copper metallodrugs promote NCI-60 chemotherapy via singlet oxygen and superoxide production with tandem TA/TA and AT/AT oligonucleotide discrimination" in the Oxford journal, Nucleic Acid Research. The work showed how di-nuclear metal complexes with artificial nuclease activity promote cancer cell death and selectively bind DNA sequences with TA/TA or AT/AT steps. The compounds were active against solid epithelial cancer cells from the National Cancer Institute’s 60 human cell line panel (NCI-60) indicating exciting future therapeutic applications for this class of molecule.

4th Network Meeting – University of Oxford

PIs and ESRs were reunited from 19 - 21 March 2018 for the third Annual ClickGene Meeting in Oriel College at the University of Oxford (UOXF). Organised by the ClickGene partners UOXF and ATDBio, the annual meeting included workshops, industry and laboratory visits, keynote lectures and ESR presentations.

On the first day, Dr. Jeanette Müller from accelopment AG provided the ESRs with an expert training session on European Grant Application Writing. ESRs were informed about existing EU funding opportunities for young researchers and different steps related to proposal writing. In the afternoon, ESRs had the opportunity to visit the premises of the companies ATDBio Ltd. and Oxford Nanopore Technologies in the Oxford Science Park and they also had the opportunity to visit the research laboratories of Prof. Tom Brown in UOXF.

During the second day, ESRs, PIs and others attended nine cutting-edge lectures by ClickGene PIs and researchers from the UOXF as follows:

Tom Brown, Department of Chemistry, UOXF

“Clicking DNA”

Chrys Chatgilialoglu, CNR

“Our radical approach to biomimetic chemistry.”

Andrew Kellett, Dublin City University

“Molecular Methods for Probing Non-Covalent Metallodrug-DNA Interactions”

Rebecca Andrews, Department of Physics, UOXF

“A single-molecule sequencing method based on DNA binding”

Jonathan Doye, Department of Chemistry, UOXF

“Coarse-grained modelling of DNA”

Graham McClorey, Department of Physiology, Anatomy and Genetics, UOXF

“Cell-Penetrating peptides to enhance oligonucleotide delivery”

Andrew Turberfield, Department of Physics, UOXF

“Molecular machinery from DNA”

Jack Hardwick, Department of Chemistry, UOXF

“F-DNA: A new form of the DNA Double Helix”

Thomas Carell, LMU Munich

“DNA bases beyond Watson and Crick”

On the third and last day, each ESR presented recent advancements in their research projects with the other ESRs and the ClickGene PIs. The ClickGene coordinator Andrew Kellett held a presentation on the status of the ClickGene project, in its last months before completion. A board meeting reuniting PIs and ESR representatives put an end to this 3-day event.

The next network meeting will take place in Dublin, Ireland by the end of the year. Information will follow in due time.

ClickGene presented results at SCNAC 2017

5 ESRs presented their project and results during the 17th Symposium on Chemistry of Nucleic Acid Components in Český Krumlov, Czech Republic. The conference included 52 oral presentations and 97 poster presentations from 5 to 7 June 2017. It was hosted by one of the ClickGene partners, the Institute of Organic Chemistry and Biochemistry AS CR.

ESRs presented the following posters:

 

ClickGene PIs and ESRs attend Symposium on Chemistry of Nucleic Acid Components

Most of the ClickGene PIs and ESRs will be attending the 17th Symposium on Chemistry of Nucleic Acid Components (SCNAC) in Český Krumlov, Czech Republic, held in June of this year. Last year’s event attracted more than 150 participants from 21 countries. The programme consists of 10 plenary lectures, 4 "Emerging young investigator" invited lectures, ca. 40 short oral presentations and a poster session.

Supervisor Michal Hocek to chair the symposium

Michal Hocek, supervisor of two ESRs for ClickGene, is the chairman of the SCNAC symposium. Michal’s main research areas include the chemistry of nucleobases, nucleosides, nucleotides and nucleic acids and his ESRs are studying in the area of genome editing and gene knockout.

Invited speakers

The list of invited speakers includes Thomas Carell of the Ludwig-Maximilians-University Munich, Germany. Thomas is, like Michal, the supervisor of two ESRs for the ClickGene project. Additionally, he is the lead of WP1 Materials for Genome Editing. Other speakers include Cynthia Burrows from the University of Utah, Kurt Vesterager Gothelf from the Interdisciplinary Nanoscience Center, Aarhus University and Andreas Marx from the University of Konstanz. The full list of plenary invited speakers is available on the SNAC website.

How to attend

The registration for the event is open and available on the SCNAC website. Due to limited capacity of the venue, the registration will be restricted to ca. 150 regular participants.

baseclick GmbH launches a new and enhanced click chemistry-based kit for detecting cell proliferation

baseclick GmbH – one of the industry partners of ClickGene – is very excited to announce their latest innovation, developed within the frame of ClickGene: a new and significantly enhanced click-chemistry based EdU “DetectPro”-Kit for the analysis of cell proliferation.

The baseclick EdU Kits provide a superior alternative to BrdU and [3H] thymidine assays by incorporating the thymidine analogue EdU during DNA synthesis and then using click chemistry for detection in a variety of dye fluorescent readouts. No harsh, DNA denaturating and laborious antibody based detection is required.

The new DetectPro Kits combine all the advantages of their very popular EdU Click Kits with a brand new fluorescence enhancer system. This makes them as easy to handle and as reliable as their predecessor, while showing outstanding efficiency and greatly enhanced signal and sensitivity. With key features such as low cell number requirement paired with low signal-to-noise ratios, baseclick  is on the forefront to the ultimate goal of “low content diagnosis”.

The new DetectPro Kits will be offered for three different readout systems: cell proliferation analysis by imaging, by flow cytometry and by high throughput screening analysis (HTS). Please visit the baseclick GmbH website for more detailed information on their new click-chemistry based tool.

 

Typical EdU cell proliferation assay: Incubation of HeLa cells for 30 minutes with EdU followed by click reaction guided detection using fluorescence microscopy. While in baseclick's standard EdU cell proliferation assay at such short exposure times (here 15 ms) only show very light signals of proliferating cells (middle image), the newly invented EdU DetectPro assay (right image) is able to detect cell proliferation with even higher efficiency and sensitivity with minimal background.

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