Grice Group
Research Projects
Dr Darren Grice
Research Leader
Dr Grice is focused on the design, synthesis and evaluation of novel carbohydrates and other potentially therapeutic molecules. Additionally, he works on carbohydrate structures from Gram-negative bacteria, plants and fungi, with the aim of developing applications for health and disease-related treatments.
Grice group bio
The Grice group are advancing the synthesis of a novel leukaemia conjugate, along with cancer therapeutics and analogues of a potent antiviral natural product. Biological evaluations are accompanying these studies. Additionally, in collaboration they have recently assembled a carbohydrate-based conjugate vaccine aimed at protecting against the principal causative Gram-negative pathogens responsible for acute Otitis media (middle ear infection) and associated respiratory diseases. A mice immunogenicity challenge study indicates that the vaccine candidate elicits a cross-reactive and protective response - an exciting basis for further ongoing development.
Research Projects: Grice group
Development of a new vaccine to prevent middle-ear infection in Australian indigenous children
Supervisors: Dr Darren Grice, Dr Ian Peak and A/Prof Jenny Wilson (School of PAM)
Australian Indigenous children suffer chronic middle ear infection at amongst the highest rates in the developed world. Individuals and communities experience long term health, social, educational and economic consequences resulting from this infection. Developing an effective vaccine could prevent such infections, alleviate suffering and widen future life opportunities for all Australian children, particularly Australian Indigenous communities.
This project will expand on our successful pilot program in which we developed a novel conjugate vaccine that targets two of the main bacteria that cause middle ear infection in children, namely, Moraxella catarrhalis (Mcat) and Non-typeable Haemophilus influenzae (NTHi).
Techniques: immunology (including ELISA), microbiology, bacterial pathogenesis, biochemistry, NMR
Exploring the immuno-modulatory effect of fungal b-glucans
Supervisors: Prof Joe Tiralongo & Dr Darren Grice
Separation Chemistry, Immunology, Glycobiology
Mushrooms are increasingly attracting attention for their immuno-modulatory activities, which are primarily due to b-glucans. b-Glucans comprise a group of glucose (Glc) polysaccharides that are chemically diverse, with a common b-glucan being cellulose (b-(1,4)-linked Glc. It is non-cellulosic b-glucans, mainly b-(1,3)-linked Glc that have been shown to be potent immunological stimulators in humans, and some are now used clinically in China and Japan, as well as being commercially available in Australia.
Due to the complexity of b-glucan chemistry and structure a detailed understanding of the mechanism of action, specifically the structural components that dictate specific immunological responses, are yet to be fully resolved. In collaboration with Integria Healthcare, the overall objective of the project is to explore the immuno-modulatory effects of mushroom b-glucans, specifically the project aims to structurally characterise commercially available mushroom polysaccharides rich in b-glucans and correlate this with their associated immuno-modulatory effects The outcomes from this project will lead to a clearer understanding of the properties of b-glucans associated with commercially available mushroom polysaccharides that induce specific immuno-modulatory effects.
Techniques: Carbohydrate chemistry, ELISA assays, separation chemistry, polysaccharide structure determination
Supervisors: Dr Darren Grice & Dr Jennifer Wilson (School of Medical Science)
Molecular Microbiology, Medicinal Chemistry
Almost all children suffer from middle ear infections (otitis media) at some point in their lives. In Australia, otitis media is particularly prevalent in Aboriginal children, and occurs very early in life. The bacteria most commonly associated with otitis media are Streptococcus pneumoniae, Moraxella catarrhalis (Mcat), and non-typeable Haemophilus influenzae (NTHi).
Gram negative bacteria such as Mcat have a layer at the outer surface that is predominantly made up of carbohydrates (oligosaccharide) attached via a membrane-embedded lipid (lipid A). The carbohydrate-lipidA molecule is known as lipo-oligosaccharide (LOS). The immune system of an infected person recognises and responds to the LOS of many bacteria, (including M. catarrhalis).
Previously we have structurally characterised Mcat oligosaccharides from mutant M. catarrhalis bacteria. Now we want to assess the biological activity of the lipooligosaccharide produced by the mutant bacteria and investigate whether there is a correlation between the structure of the oligosaccharide and its toxicity. Methods to evaluate the biological activity of the mutant LOS will include growth rate, toxicity and susceptibility to hydrophobic reagents as compared to wildtype.
Analysis of lipopolysaccharide structures from Moraxella bovis
Supervisors: Dr Darren Grice, Dr Ian Peak & Dr Jennifer Wilson (School of Medical Science)
Medicinal Chemistry, Molecular Microbiology
The aim of this project is to isolate carbohydrate components from the bacteria Moraxella bovis and determine the structures of these carbohydrate molecules. Moraxella bovis causes infectious bovine keratoconjunctivitis (IBK) in cattle, causing significant loss of weight and permanent blindness. Vaccine therapies have been unsuccessful in treating these infectious agents. Obtaining structural carbohydrate information will enable future studies to determine the role of these carbohydrates in disease and develop potential new vaccine strategies.
The project will require the development of knowledge and skills in the areas of cell culture, chemical and biochemical extraction and manipulation strategies, nuclear magnetic resonance (NMR) and mass spectrometry (MS) of isolated carbohydrate materials.
Identification of a capsular polysaccharide from Moraxella bovis. J.C. Wilson, P.G. Hitchen, M. Frank, I.R. Peak, P.M. Collins, H.R. Morris, A. Dell and I.D. Grice. Carbohydr. Res. 2005, 340(4), 765-769.
Analysis of surface carbohydrate structures from Gram-negative Moraxellaceae bacteria
Supervisors: Dr Darren Grice, Dr Ian Peak & Dr Jennifer Wilson (School of Medical Science)
Medicinal Chemistry, Molecular Microbiology
The aim of this project is to isolate surface carbohydrate components from bacteria in the Moraxellacae family, then determine the structures and biological significance of these carbohydrate molecules. Many bacteria in this family are commensals of the human upper respiratory tract and are important in protecting against disease. Obtaining structural carbohydrate information will enable us to determine the role of these carbohydrates, and potentially developing new strategies to promote upper-respiratory tract health.
The project will require the development of knowledge and skills in the areas of cell culture, chemical and biochemical extraction and manipulation strategies, nuclear magnetic resonance (NMR) and mass spectrometry (MS) of isolated carbohydrate materials.
1. De Castro, Grice, Daal, Peak, Molinaro, Wilson. Carb. Res. (2014) 388:81-86.
2. Wilson, Hitchen, Frank, Peak, Collins, Morris, Dell and Grice. Carb. Res. (2005) 340:4, 765-769.
Development of novel phthalic acid diesters as potential human parainfluenza virus therapeutics
Supervisors: Dr Darren Grice, Dr Andrew Pearson (School of Medical Science) & Assoc Prof Evelin Tiralongo (School of Pharmacy)
Medicinal Chemistry
Infectious diseases, such as Dengue (DENV), Chikungunya (CHIKV) and Human parainfluenza virus (hPiV3), are a major cause of avoidable mortality and morbidity, particularly for children in developing countries. However, due to the rapidly mutating nature of viruses, resistance to conventional drug therapies occurs. The proposed research project is ongoing and follows on from our previous work where we isolated a chemical compound from a Bangladeshi mangrove fern Acrostichum aureum that showed potent activity particularly against hPiV3, but also moderate activity against DENV2 and CHIKV. This project aims to synthesise the isolated compound and also synthesise analogues where chemical groups have been varied, then test these compounds for potency as potential anti-viral agents against hPiV3, DENV2 and CHIKV. It is hoped that this work will lead to the identification of a new agent with potent antiviral.
Uddin, Bettadapura, Guilon, Grice, Mahalingam, Tiralongo. J. Antivir. Antiretrovir. (2013) 5:6.
Degradation of cancer-associated proteins using proteolysis targeted chimeras (PROTACs)
Supervisors: Dr Darren Grice & Prof Mark von Itzstein
Medicinal Chemistry
From previous studies1,2, it is clear that the use of Proteolysis-targeting chimera (PROTAC) molecules can result in the effective degradation of target-proteins. PROTAC techniques involve the exploitation of normal protein degradation essential for cellular maintenance and hijacking the system to specifically target proteins of interest (POI) for degradation.
To achieve an effective PROTAC design the molecule must provide high affinity binding to both the protein of interest and a suitable ubiquitin ligase and maintain these interactions whilst not inhibiting the overall ubiquitination (or tagging for destruction) process.
Work is underway within the Institute for Glycomics to synthesise novel PROTAC molecules to achieve the successful proteolysis of a cancer-associated protein, which is known to be intimately involved in cancer progression. This research will be further progressed in this ongoing project.
Techniques: The project will involve synthetic organic/carbohydrate chemistry, along with NMR spectroscopy, mass spectrometry and other associated techniques for structural characterisation of the synthesised PROTACs followed by assessment of biological activity.
1. Winter, et al. Science. (2015) Jun 19;348(6241):1376–81.
2. Gu, Cui, Chen, Xiong, Zhao. (2018). Bioessays Apr 40(4), e1700247.
Development of Novel Antibacterial Treatments
Supervisors: Assoc Prof Todd A Houston, Dr Darren Grice, Assoc Prof Nick West (U.Queensland)
Medicinal Chemistry
Deadly infectious bacteria such as Mycobacterium tuberculosis and MRSA are able to survive within macrophages in a human host and this makes treatment particularly challenging. Incomplete or ineffective antibiotic treatment leads to development of drug resistant bacteria, a problem of growing global concern. We are currently developing antibacterial compounds that can be formulated into nanoparticles with drug targeting epitopes to improve uptake and drug delivery into macrophages. This allows for improved bactericidal activity and diminishes the opportunity for the development of drug resistance.
Techniques: Synthetic carbohydrate chemistry; liposome formulation; bacterial cell growth assays.
Interested in any of these research projects?
Get in touch with Dr Darren Grice to discuss your next research opportunity