Inorganic Dublin 2017, Trinity College Dublin

Inorganic Dublin 2017 was held in the in the Science Gallery in TCD on 13th December 2017. Zara, Creina and Nicolo attended and presented their research projects during the evening poster session with Zara taking home the prize for best poster!

Presentations from the Kellett group included:

  • Zara Molphy — [Cu2(tetra-(2-pyridyl)-naphthalene)Cl4] Displays Non Intercalative Major Groove Binding and Self-Activating Oxidative DNA Damage (Poster presentation)
  • Creina Slator — Di-Copper Metallodrugs Promote NCI-60 Chemotherapy via Singlet Oxygen and Superoxide Production with Tandem TA/TA and AT/AT Oligonucleotide Discrimination (Oral and poster presentation)
  • Nicolo Fantoni — Caged Copper (II) Oxidative Chemical Nucleases

DNA Damage and Repair: Computations Meet Experiments

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Members of the group travelled to the Lorentz Center at Leiden University, Netherlands to take part in a DNA Damage and Repair workshop hosted by collaborators Antonio Monari, Jean-Luc Ravanat and Elise Dumont (October 30th - November 03rd 2017). The workshop lasted 5 days and allowed participants to discuss their research in depth, through a combination of informal talks, working sessions, and discussions.

Presentations from the Kellett research group included:

  • Andrew Kellett – Polynuclear Metallodrug — Nucleic Acid Interactions: New Therapeutic and Biochemical Applications (Oral presentation)
  • Zara Molphy / Creina Slator / Andrew Kellett — [Cu2(tetra-(2-pyridyl)-naphthalene)Cl4] Displays Non Intercalative Major Groove Binding and Self-Activating Oxidative DNA Damage (Oral and poster presentation)
  • Creina Slator / Zara Molphy / Andrew Kellett — Di-Copper Metallodrugs Promote NCI-60 Chemotherapy via Singlet Oxygen and Superoxide Production with Tandem TA/TA and AT/AT Oligonucleotide Discrimination (Oral and poster presentation)

Thanks to Antonio Monari and the organising committee for the invitation to participate!

XVII Symposium on Chemistry of Nucleic Acid Components (SCNAC)

In June 2017, members of the Kellett research group and the ClickGene ETN attended the historic XVII Symposium on Chemistry of Nucleic Acid Components (SCNAC) in the beautiful town of Cesky Krumlov, a UNESCO World Heritage Site in the Czech Republic.

Contributions to this conference covering 5 main themes: (i) organic synthesis of nucleosides, nucleotides and oligonucleotides, (ii)medicinal chemistry and pharmacology, (iii) biochemistry and chemical biology of nucleic acids and (v) nucleic acids based functional molecules and materials.

Plenary lectures were delivered by collaborators Prof. Tomas Carell and Prof. Michal Hocek (Organiser) with almost 100 posters were presented by postgraduate students and postdoctoral researchers.

Presentations from the Kellett group included:

  • Andrew Kellett – Polynuclear Metallodrug — Nucleic Acid Interactions: New Therapeutic and Biochemical Applications (Oral presentation)
  • Nicolo Fantoni, Zara Molphy / Andrew Kellett – Artificial Metallo-Nucleases for Gene Editing (Poster presentation)
  • Creina Slator / Zara Molphy / Andrew Kellett — Di-Copper Complexes Promote NCI-60 Chemotherapy by Intracellular Superoxide and Singlet Oxygen Facilitated DNA Damage (Poster presentation)

Postgrads and postdocs enjoyed a paddle down the Vltava River and exploring Český Krumlov town and Castle. Thanks to Michal Hocek and his team at the Institute of Organic Chemistry and Biochemistry (IOCB, Prague) for a great week of nucleic acid chemistry.

DCU Chemistry Research Day Success!

The DCU School of Chemical Sciences Chemistry Day was held on Friday May 12th. Postgraduate students, Natasha McStay and Nicolo Fantoni presented work from their respective PhD research projects, with Natasha winning the Colin Barnes Prize for Outstanding Postgraduate Research!

Our final year research student, Sinead O'Carroll was one of five undergraduate students to be selected from the outgoing Chemical & Pharmaceutical Sciences and Analytical Science courses to present work conducted in the Kellett research group over her 12-week project working alongside Nicolo!

A great day (and night) was had by all group members and a special thanks goes out to the organising committee!

Opioid Architectures as New DNA Binding Molecules

We have recently published an article entitled “C3-Symmetric Opioid Scaffolds are pH-Responsive DNA Condensation Agents” in the Oxford journal, Nucleic Acid Research. In this article, we report the synthesis of novel tripodal C3-symmetric opioid scaffolds as high-affinity condensation agents of duplex DNA. Through our collaboration with Prof. Nicholas Gathergood (Tallinn University of Technology, Estonia), we achieved the synthesis of these novel opioid structures and evaluated the synthesis through green chemistry metrics, highlighting key synthetic aspects for future work. The opioid scaffolds were identified through agarose electrophoresis, viscosity, and turbidity as effective condensation agents of both supercoiled and canonical B-DNA structures. In collaboration with Prof. Attilio Cafolla (School of Physical Sciences, DCU) we have achieved high-resolution atomic force microscopy (AFM) images of the morphological changes of DNA through the condensation affects of these opioid molecules. In the presence of low (mM) drug loading, supercoiled pUC19 DNA exhibited small cluster formation were tight packed is observed at the cluster centre, as the concentration is gradually increased large tightly packed globules of DNA is formed, supporting earlier gel electrophoresis analysis. The tripodal opioid condensation was identified as pH dependent and through thermal melting and circular dichroism; evidence of cationic-phosphate backbone coordination was identified. Further studies by on-chip microfluidic analysis provided concentration-dependent inhibition to site selective excision by type II restriction enzymes. In summary, this work has revealed the discovery of a new high-affinity DNA binding scaffold capable of mediating condensation ostensibly through electrostatic and H-bonding interactions with the phosphate backbone.

This publication has recently made news headlines on the Dublin City University website.

   
  
 
  
    
  
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     AFM images of MC3-treated supercoiled and HindIII linearised pUC19 DNA;  A-D : supercoiled pUC19 with 8, 9, 10, and 20 μM  MC3 ;  E-H : linear pUC19 with 5, 10, 20, and 50  m M  MC3 .

AFM images of MC3-treated supercoiled and HindIII linearised pUC19 DNA; A-D: supercoiled pUC19 with 8, 9, 10, and 20 μM MC3; E-H: linear pUC19 with 5, 10, 20, and 50 mM MC3.

35th ChemEd-Ireland Conference

Integrating Research and Practice in Chemistry Teaching and Learning

The Centre for the Advancement of STEM Teaching & Learning (CASTeL) today (22nd October) hosted the 35th ChemEd-Ireland conference at Dublin City University with the Kellett group and H2020 ITN project ClickGene involved throughout. The theme of the ChemEd-Ireland conference was “Integrating Research and Practice in Chemistry Teaching and Learning” that allowed chemistry school teachers gain new knowledge in area of chemistry research and in practical research skills. A number of seminars were given at the meeting, including one by Dr. Andrew Kellett on “Inorganic Chemistry in Medicine”. Afterward, teachers had the chance to access our laboratories both in the NICB and NRF buildings, shadowing our postdoctoral and postgraduate researchers in some bioinorganic and synthetic chemistry related experiments. Here they had the opportunity to synthesize Sigman’s salt [Cu(Phenanthroline)2]+ (CuPhen) and learn how this agent acts to damage DNA by free radical oxidation. Furthermore, teachers had an opportunity to learn about ‘Click Chemistry’ promoted by the copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) reaction and these reactions represent some of the fundamental science behind the ClickGene project. The teachers experienced some further analytical techniques by using UV-Vis to detect and quantify the presence of various duplex DNA polymers. Finally, a workshop for the detection of DNA oxidative damage by gel-electrophoresis was run within the NICB molecular biological laboratories.

Dr Andrew Kellett receives SFI CDA award

Science Foundation Ireland (SFI) Career Development Award

SFI have awarded Dr Andrew Kellett a prestigious Career Development Award (CDA). The project, Polynuclear Platinum(II) Biomaterials (PPtBio) for Antisense Therapeutic Application and Detection of Human Genetic Disease, will begin in December of 2016 and involves collaborators:  Prof Nicholas P Farrell (Virginia Commonwealth University, USA), Prof Tom Brown (University of Oxford), Dr Niall Barron (Director of NICB, DCU, Ireland), and ATDBio Ltd. (Oxford and Southampton, UK). A total award of €642,150 for the PPtBio project was announced today (October 18th) by Minister of State for Training, Skills and Innovation, John Halligan TD. Full details can be found here: http://www.sfi.ie/news-resources/press-releases/minister-halligan-announces-research-investment-of-€22.3-million-in-next-generation-of-research-talent.html.  

 From Left to Right: Jiafu Wang, Susan Kelleher, Professor Greg Hughes, Director General of Science Foundation Ireland and Chief Scientific Adviser to the Government of Ireland, Professor Mark Ferguson, Andrew Kellett, Minister of State for Training, Skills and Innovation, John Halligan TD, James Walsh, Prince Anandarajah, Robert Forster, Jianghui Meng, Professor Oliver Dolly, Kevin McGuiness

From Left to Right: Jiafu Wang, Susan Kelleher, Professor Greg Hughes, Director General of Science Foundation Ireland and Chief Scientific Adviser to the Government of Ireland, Professor Mark Ferguson, Andrew Kellett, Minister of State for Training, Skills and Innovation, John Halligan TD, James Walsh, Prince Anandarajah, Robert Forster, Jianghui Meng, Professor Oliver Dolly, Kevin McGuiness

Prof. Bernard Golding visits DCU

Professor Bernard T. Golding Seminar

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 Molecular structure of Rucaparib

Molecular structure of Rucaparib

Professor Golding of Newcastle University and NewChem Technologies today (Oct. 14th) visited DCU and two of our research centres, the NICB and NRF.  He delivered an excellent seminar on "Design, Synthesis and Biological Activities of Novel Anticancer Agents" where he spoke of his research at Newcastle that has led to potent inhibitors of cyclin dependent kinase 2 (CDK2) and poly(ADP-ribose) polymerase (PARP). This research led directly to the discovery of potent small molecule PARP inhibitors and initiation of a pre-clinical collaboration with Agouron Pharmaceuticals (San Diego) resulted in the identification of rucaparib, the first-in-class PARP inhibitor for clinical evaluation in cancer patients. More than 200 patients have received this Newcastle-Agouron drug rucaparib and in the earliest clinical trials (2003 and 2005), some patients had a life expectancy of only a few months, but of these seven most are still alive and cancer-free. 

Creina Slator wins best poster prize

Creina Slator wins best overall poster at the 1st Medicinal Chemistry Conference of Ireland

Congratulations to Creina on winning a poster prize at the 1st Medicinal Chemistry Conference of Ireland!! The meeting was held at the TBSI in Trinity College Dublin today (July 1st) and featured a range of international and national speakers along with over 50 poster presentations. Poster prizes were kindly sponsored by Catalent.