Tim O'Sullivan

Dr Tim O’Sullivan received his BSc Degree in Industrial Chemistry from the University of Limerick in 1997. He then went on to do a PhD in natural products synthesis under the supervision of Prof. Lew Mander at the Research School of Chemistry of the Australian National University from 1998 to 2001.

He worked as a postdoctoral researcher on the synthesis of anti-cancer Tamoxifen analogues with Prof. Mary Meegan in Trinity College Dublin from 2001 before taking up another postdoctoral fellowship with Prof. Pat Guiry in University College Dublin on the synthesis of novel anti-inflammatory Lipoxin analogues in 2003. Following a period as research manager in UCD, he was appointed as Lecturer in Pharmaceutical Chemistry in the Schools of Pharmacy & Chemistry in UCC in 2006 and Senior Lecturer in 2023. 

He is a member of the Royal Society of Chemistry, the Marie Curie Alumni Association and COST Action 'CA21145 European Network for diagnosis and treatment of antibiotic-resistant bacterial infections (EURESTOP)'.

He was previously a member of COST Actions 'CA16107 EuroXanth' and 'CM1307 Targeted chemotherapy towards diseases caused by endoparasites'. 
Recent news:
See our LinkedIn Profile for recent updates.

Design and Synthesis of Novel Bioactive Compounds
Our research is focused on developing new strategies for the synthesis of bioactive compounds. The underlying goal in this work is to improve upon existing techniques and to discover novel methods for assembling complex molecular targets. Ultimately, we aim to apply this knowledge to the development of more potent analogues of existing compounds, with a view to producing pharmaceutically relevant therapeutic agents.

Development of Quorum Sensing Inhibitors - Disrupting Antimicrobial Resistance
Cystic Fibrosis (CF) is an inherited disease which affects about 1,500 Irish people. CF causes the body to produce an abnormally sticky fluid in the lungs which makes CF patients susceptible to serious bacterial infection. CF patients are faced with frequent stays in hospital as they are prone to infection by antibiotic-resistant bacteria. Approximately 60% CF patients have a chronic respiratory infection caused by multiple bacteria that settle into the thick mucus trapped in the airways. These bacteria have evolved a special type of defence where they excrete a chemical messenger on treatment with an antibiotic. These chemical messengers are cis-2-unsaturated fatty acids, with the most important being Diffusible Signal Factor (DSF). DSF leads to increased biofilm formation and resistance to antibiotics, factors that prolong the infection. We are developing sulfonamide-based mimics which counteract the effects of DSF and, thereby, shut down the bacterias’ defence mechanism.

We are also investigating halogented furanones as inhibitors of the Autoinducer-2 (AI-2) quorum sensing system. Our work has demonstrated how novel chloro-, bromo- and iodo-containing furanones can effectively disrupt resistance in AI-2-sensitive pathogens.

Antimicrobial IMPDH Inhibitors
Inosine 5′-monophosphate dehydrogenase (IMPDH) is an essential enzyme in guanine nucleotide biosynthesis. Recent research has confirmed that IMPDH respresents a promising target for the discovery of new antimicrobial agents. Unfortunately, current IMPDH inhbitiors are not especially stable in vivo, resulting in limited clinical application. We have developed novel bioisosteric analogues, replacing unstable oximes with stable heteroaryl rings, which demonstrate increased stability while retaining their activity against the IMPDH enzyme. We are currently investigating other structural modifications, such as the incorporation of a squaramide group in place of the more common urea functionality.

Novel Anti-viral Therapies
There is a huge demand for new anti-retroviral drugs to increase patients treatment options, especially for drugs with enhanced safety profiles that display reduced side-effects and which are competitively priced. Given that NRTIs (Nucleotide Reverse Transcriptase Inhibitors) are widely used in first-line treatment in combination therapies, we are investigating their mode of action at a molecular level with the aim discovering  more potent NRTIs. NRTIs function by prematurely terminating the HIV life cycle. A key step in this process involves the in vivo cleavage of the very strong Phosphorous-Oxygen bond which is either present in the original NRTI (e.g. Tenofovir) or is added by in vivo phorsphorylation. We believe that a more efficient inhibitor should result if the stronger Phosphorous-Oxygen bond is replaced with a more labile Phosphorous-Sulfur bond . The P-S bond is considered a bioisostere of the P-O bond, thus representing an excellent candidate for strategic substitution.

Stable Resolvin Analogues as Potent Anti-inflammatories
Resolvins are polyunsaturated fatty acid-derived molecules which play an important role in the resolution of inflammation. They are termed specialised pro-resolving mediators (SPMs) and faciliate a return to homeostasis following an inflammatory response. These molecules are currently the focus of intensive research, with the aim of developing potent anti-inflammatory agents. However, natural resolvins undergo rapid metabolic deactivation in vivo, in part due to the presence of a reactive polyene system. Our research involves the creation of metabolically stable resolvin analogues and working with international collaborators to evalulate their biological activity.

Current PhD Students

Previous PhD Students

Previous Postdoctoral Researchers

Postgraduate and postdoctoral positions:

We welcome applications from suitably qualified candidates seeking PhD funding via Research Ireland Postgraduate Scholarship Scheme or the UCC Eli Lilly Scholarship Scheme.

We also welcome application from candidates seeing postdoctoral funding via EU Marie Curie Fellowships or Research Ireland Postdoctoral Fellowships.

Currently

PF1009 - Introduction to Pharmaceutical Chemistry (Module Coordinator)

PF2012 - Pharmaceutical Analysis (Module Coordinator)

PF3012 - Respiratory, Musculoskeletal and Dermatology Systems

CM3001 - Organic Synthesis, Intermediates and Heterocycles

CM4001 - Advanced Organic Synthesis and Reactivity (Module Coordinator)

CM7005 - Theory and Application of Computational Chemistry (Module Coordinator)

Previously

CM1100 - History of Chemistry

CM1005 - Introductory Chemistry for Food and Nutritional Scientists

CM3110 - Pharmaceutical Solids and Technology

CM3028 - Scientific Communication and Information Literacy Skills