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We have two fully funded PhD positions availble in hybrid drug screening and development.
Application deadline: Janurary 05th 2024.
Position 1 - in collaboration with Dr. Alex Eustace (School of Biotechnology, DCU): download here.
Apply here: https://euraxess.ec.europa.eu/jobs/177011
Position 2 - in collabtaion wtih Dr. Creina Slator and Dr. Una Prendergast (Nano Research Facility, DCU): download here.
Apply here: https://euraxess.ec.europa.eu/jobs/177010
Prof. Andrew Kellett was awarded the 2023 DCU President’s Research Medal within the field of “Natural Sciences, Health, Engineering and related areas”. Prof. Kellett led multiple research projects spanning chemical sciences and chemical biology. Prof. Kellett is the co-ordinator of the NATURE-ETN Project which seeks to extend the boundaries of molecular medicine and provide new tools for treating cancer and monogenetic diseases. The network includes ten beneficiaries and seven partner organisations, including nine leading research institutions, five cutting-edge SMEs and three multinationals. Andrew’s work has also been recognised externally with prestigious prizes from Enterprise Ireland and the Science Foundation Ireland Research Centre for Pharmaceuticals.
Andrew Kellett was recently interviewed by Claire O’Connell for the Irish Times on the 2022 Nobel Prize in Chemistry, which was awarded to Barry Sharpless, Morton Meldal and Carolyn Bertozzi for the development of Click Chemistry and Bioorthogonal chemistry. Andrew discussed the significance of Click Chemistry, and how his research group employs the ‘click’ method for the development of novel gene-targeted therapeutics.
https://www.irishtimes.com/science/2022/12/01/click-and-collect-the-nobel-prize-in-chemistry/
PhD Positions
We have two fully funded PhD positions in hybrid drug development available (deadline: October 14th)
We have two fully funded PhD positions in hybrid drug development available:
Position 1: Download the advert here.
Position 2: Download the advert here.
EURAXESS links:
Position 1: https://euraxess.ec.europa.eu/jobs/834121
Position 2: https://euraxess.ec.europa.eu/jobs/834119
Application procedure:
Applications must be emailed to andrew.kellett@dcu.ie and contain a cover / motivational letter, full CV, and a list of three suitable referees.
Deadline: October 14th 2022.
Andrew Kellett has been awarded the SSPC Investigator of the Year!
The SSPC is the Science Foundation Ireland (SFI) Research Centre for Pharmaceuticals, a world-leading hub of Irish research expertise developing innovative technologies to address key challenges facing the pharmaceutical and biopharmaceutical industry.
Full details here: https://sspc.ie/andrew-kellet-secures-sspcs-directors-award-for-investigator-of-the-year/
Our group at Dublin City University in collaboration with ATDBio Ltd. and University of Oxford have developed a new method for the design of novel platinum drug – nucleic acid hybrids as antisense therapeutics.
The development of this method is founded on the use of ‘click chemistry’ and involves the independent synthesis of biologically active platinum(II) drugs containing azide-modified scaffolds and alkyne-modified triplex forming oligonucleotides (TFOs). Employing click chemistry strategies, these substrates were combined through bioconjugation to generate a library of active platinum(II)-nucleic acid hybrids that present opportunities as gene-targeting agents.
Platinum-based metallodrugs have formed the mainstay of cancer therapeutic regimens however resistance and dose-limiting toxicity issues still to this day present a significant challenge for their use in combatting recalcitrant cancers such as triple-negative breast cancer or glioblastoma multiforme.
A major aspect of this challenge is to prevent off-target specificity of the metal-based drug agent. To enhance target discrimination, short nucleic acid sequences known as TFOs were employed as gene-directing probes. These sequences are designed to only target gene tracts of interest and prevent off-targeting issues.
Working in collaboration with Prof. Tom Brown and his team based in ATDBio Ltd., platinum(II)-TFO hybrids were developed that demonstrated precise targeting of the green fluorescent protein (GFP) gene. The work affords a novel modular approach for the preparation of platinated TFOs, provides precise triplex formation and subsequently demonstrated specific targeting and crosslinking of targets of interest without specificity issues.
The results are very exciting and represent the first examples of platinum(II)-TFO hybrids designed using this methodology. Future approaches to fully realise the biological potential of these platinum(II) hybrids within antisense technology may involve the use of a number of DNA base modifications such as phosphorothioate backbone linkages. These modifications must be combined with a unique targeting strategy, whereby mutant genes or oncogenes are specifically targeted by this technology to achieve selectivity over normal cells.
Dr. Andrew Kellett, Associate Professor of Inorganic and Medicinal Chemistry in DCU School of Chemical Sciences, Principal Investigator of Biodesign Europe, and Funded Investigator of the SSPC and CÚRAM SFI Research Centres, is the corresponding author of the study. The paper “A Click Chemistry Approach to Targeted DNA Crosslinking with cis-Platinum(II)-Modified Triplex Forming Oligonucleotides” has been published in the journal Angewandte Chemie and is an open access publication.
Our group at Dublin City University in collaboration with Chalmers University of Technology (CUT), Sweden, have discovered a new method to prepare DNA damaging drug molecules. The long-term goal of the work aims to provide effective new personalised cancer treatments with lower side effects.
The method is called ‘Click and Cut’ and involves the attachment of metal ion binding groups to a central scaffold using click chemistry. Using this approach, the team prepared a library of drug candidates and identified a lead agent with high potential for treating human cancer.
Metal-based drugs deliver first-line treatment against many forms of cancer, but resistance often builds up leading to their inactivation. To widen treatment possibilities, particularly against difficult-to-treat cancers such as triple-negative breast cancer or glioblastoma multiforme, new therapies with improved or evasive modes of action are highly sought after.
To address this challenge our developed the ‘Click and Cut’ method and screened the resulting drug library together with different types of metal ions. From the entire screen, one compound was identified to bind strongly with copper ions and produce a unique type of DNA damage that is not possible to achieve with existing metal-based drugs.
In collaboration with Prof. Fredrik Westerlund and his team at CUT, the compound was then identified to produce DNA damage within primary human cells. By isolating the DNA from these cells, single molecule imaging was performed to visualise the amount of damage and the type of DNA repair (base excision repair - BER) enzymes activated in response. The results were encouraging and showed the compound could produce a high amount of specific damage which placed it in a unique chemotherapeutic class.
Dr. Andrew Kellett, Associate Professor of Inorganic and Medicinal Chemistry in DCU School of Chemical Sciences, Principal Investigator of Biodesign Europe, and Funded Investigator of the SSPC and CÚRAM SFI Research Centres, is the corresponding author of the study. The paper “Click and Cut: A Click Chemistry Approach to Developing Oxidative DNA Damaging Agents” has just appeared in the journal Nucleic Acids Research and is an open access publication.
Speaking about the discovery, Dr. Andrew Kellett said:
“These results are promising and indicate a new avenue for preparing unique types of drug molecules. Although click chemistry has an extensive range of applications—particularly in the field of nucleic acid chemistry—it has not yet been widely considered as a way to construct DNA-damaging metallodrugs.”
Our team now aims to expand this method and develop new therapies directed to specific cancer-causing genes. Plans are also underway to develop second generation chemotherapeutics with improved properties.
About Biodesign Europe
Biodesign Europe combines the research strengths of Dublin City University and Arizona State University, two leading institutions striving to make much-needed scientific discoveries and innovations available to advance society. Inspired by nature’s design, particularly at the intersection of engineering, biology and computing, our scientific discoveries and innovations are being directed towards the areas of human health, community safety and global sustainability.
About SSPC
The Science Foundation Ireland Research Centre for Pharmaceuticals, SSPC, is a world-leading hub of Irish research expertise developing innovative technologies to address key challenges facing the pharmaceutical and biopharmaceutical industry.
About CÚRAM
CÚRAM, the SFI Research Centre for Medical Devices, a world leading Science Foundation Ireland research centre designing the next generation of ‘smart’ medical devices.
We have 5 positions currently available in the research group!
Postdoctoral position (24 months) available in my group at DCU School of Chemical Sciences funded by NovoNordisk Foundation in collaboration with Prof. Christine McKenzie at the University of Southern Denmark. Apply here: https://bit.ly/3kfUeIO (Deadline: Aug 10th)
Postdoctoral position (12 months) available in my group at DCU School of Chemical Sciences funded by the SSPC in collaboration with MSD Ireland. Apply here: https://bit.ly/39WxwAU (Deadline: Aug 20th)
3 Marie Skłodowska Curie ESR (Early Stage Researcher) positions now available in my group in the H2020 NATURE-ETN. Apply here: https://bit.ly/31kQRI9 (Deadline: Aug 19th)
X-ray crystallography is a highly valuable and, sometimes, essential method of analysis in chemical research. In the Kellett group, we hope to apply crystallography to our DNA targeted developmental materials to allow us to further probe binding modalities, conformational changes, structure-activity relationships and provide us with further data upon which we can base our rational design approach. One of our newest researchers, Alex Gibney travelled to the University of Southern Denmark (SDU) with Prof. Vickie McKee to visit collaborator Prof. Christine McKenzie. This trip introduced Alex to the software, equipment and methods he hopes to use in the later stages of his research. Alex would like to thank Prof. Christine McKenzie and her group for welcoming and accommodating them in Odense.
It is becoming increasingly clear that some of the most complex scientific challenges only can be achieved through interdisciplinary efforts. With the Exploratory Interdisciplinary Synergy Programme, the Novo Nordisk Foundation sought to strengthen the synergy between researchers, across disciplines, organizations and national borders. With this in mind, we assembled a new multidisciplinary consortium for this innovative project Image and Destroy: New Radionuclides for Cancer Theranostics (ID-Cancer). The team consists of Prof. Christine McKenzie (The Department of Physics, Chemistry and Pharmacy Southern Denmark University, DE), Assoc. Prof. Helge Thisgaard (Department of Nuclear Medicine, Odense University Hospital, DE) and Prof. Andrew Kellett (Dublin City University). Together we combine expertise in synthetic organic and molecular inorganic chemistry, nucleic acid chemistry, and DNA damage and repair, nuclear physics, radionuclide production, cell and small animal radioisotope uptake, clinical PET/SPECT, nuclear medicine and oncology. We aim to develop methods for enabling implementation of 119-antimony (119Sb) and 58m-cobalt (58mCo) Auger Electron Emitters (AEEs) to target and destroy of the most aggressive and deadly type of brain cancer, glioblastoma multiforme (GBM).
Nucleic Acids for Future Gene Editing, Immunotherapy and Epigenetic Sequence Modification (NATURE-ETN) is a European Training Network (ETN) project funded from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Actions co-ordinated by Prof. Andrew Kellett at DCU. Partners involved in this ETN include: accelopment AG, CH (Partner Organisation), Ludwig-Maximilian-Universität München (DE), University of Oxford (UK), Université de Recherche Paris Sciences et Lettres (FR), Ustav Organicke Chemie a Biochemie (CZ), University of Reading (UK), Uniwersytet Warszawski (PL), ATDBio Ltd (UK), Baseclick GmbH (DE) and National Institute for Bioprocessing Research and Training Ltd (IE). This multisectoral consortium is focused on nucleic acid immunotherapy, gene editing, DNA crystallography, and epigenetic DNA sequencing technology.
This ETN will leverage recent breakthrough discoveries in epigenetic manipulation, gene editing, small molecule DNA targeting, and rapid gene/transgene detection to extend the boundaries of molecular medicine and provide new tools for treating cancer and monogenetic diseases. 15 Early Stage Researchers (ESRs) trained within NATURE-ETN will acquire the necessary knowledge and skillset to fill high-functioning industry jobs in the biotechnology and biopharmaceutical industries, but also to maintain and advance Europe’s competitiveness and innovation capacity.
Read the press release from DCU here
Every January, the Kellett Group hosts a group of second level transition year students to our research laboratories in the Nano-Research Facility at DCU. Students were given a tour of the building and research infrastructure available to the group including microscopy and spectroscopy suites along with material processing and 3D printing labs. Students then took part in a 2 part hands on lab session where they were introduced to a number of concepts and experimental techniques such as DNA damage, agarose and polyacrylamide gel electrophoresis and click chemistry!
Irish Biological Inorganic Chemistry Society (IBICS-3) was hosted this year by RCSI. On the day Andrew gave a keynote lecture “Polynuclear Metallodrug-DNA Interactions: New Therapeutic and Gene-Directed Applications” while Zara presented a poster on a recently published paper in the MPDI journal Molecules. Thanks to the organising committee for a great day promoting collaboration in research areas such as biology, chemistry, physics and medicine across the county.
Two members of the Kellett research group graduated at this years Autumn conferring ceremony! Huge congratulations to Dr. Karen Ontiveros Castillo who successfully defended her PhD in August and graduated from the School of Chemical Sciences at DCU! Simon Poole carried out his 4th year project in the research group and graduated from the B.Sc in Chemical and Pharmaceutical Science programme. Simon recently joined the research group as a PhD candidate!
Members of the group attended the 1st International Workshop on Metals in Medicine at Chimie ParisTech, PSL University on the 14-15 November 2019. The aim of the workshop was to raise awareness on the extended value of metal compounds in medicine through a wide-range of world-class case studies and workshops centered on cutting edge issues. Speakers at the event included Gilles Gasser (Chimie ParisTech, PSL University, France), Gérard Jaouen (Chimie ParisTech, PSL University, France), Roger Alberto (University of Zurich, Switzerland)), Paul Dyson (EPFL, Switzerland), Christophe Biot (University of Lille, France), Bernard Keppler (University of Vienna, Austria) and Sherri McFarland (University of North Carolina at Greensboro, USA). Creina, Brionna and Zara presented posters on their research at the workshop. Thanks to Gilles for the invitation and for organising a such a great conference!
1st year PhD student Anna Ziemele has just been awarded a prestigious Irish Research Council Government of Ireland Postgraduate Scholarship for her exciting new project is entitled “Development of Mitochondrial Gene-Editing Ruthenium Hybrid Materials”.
Congratulations Anna!
The 15th RSC Nucleic Acids Forum was held at the Royal Society of Chemistry on the 12th of July in Mayfair, London. This meeting brought the UK and Irish Nucleic Acids Research community together to discuss exciting research involving the study of nucleic acids. At this event Bríonna presented a poster based on her current research which focuses on the “Development of new qPCR methodology to probe gene knockdown” while Nicoló presented his poster “Gene editing via nucleic acid ‘click’ chemistry”.
This year the 71st Irish Universities Chemistry Research Colloquium was hosted by TU Dublin & RCSI on June 20th and 21st. The colloquium was attended by PhD students Séan O’Halloran, Brionna McGorman, Anna Ziemele and Karen Ontiveros.
The RSC Organic Division Ireland Regional Meeting was held on Friday 7th June 2019 at the UCD O’Brien Centre for Science at University College Dublin where Andrew gave an invited lecture entitled “Gene editing with nucleic acid click chemistry”. On the day Zara won best poster prize which was presented by Professor Tom Simpson, University of Bristol.
A mini symposium in honour of Professors Jacqueline Barton and Peter Dervan was held in Trinity College Dublin on May 17th. Prof. Jackie Barton gave the prestigious Cocker Lecture entitled “DNA Signalling” and was also awarded the RSC Centenary Prize. Thanks to Professors Sylvia Draper, Peter Dunne, Isabel Rozas for the invite to present on “Recent Advances in Copper(II) Artificial Metallonuclease Design” at this symposium.
