‘The Strange Case of Dr Jekyll and Mr Hyde’: When good Immune cells have gone bad.
While immune cells generally play a positive role in the body and, for example, are critical in the identification and destruction of unwanted pathogens, there are instances where immune cells can exasperate disease. In the same way that the two personas the evil ‘Mr Hyde’ and the more benevolent ‘Dr Jekyll’ can switch personalities via the agency of potions, we are interested in exploring how ‘bad’ immune cells can be turned into more ‘beneficial’ cells though the agency of immunomodulators (or molecules that modify the immune response). Areas of research include switching the phenotype of the deleterious Tumour Associated Macrophages (TAMs) in the tumour microenvironment to a phenotype that can lead to better anti-cancer therapies.
The immune response to bacterial glycolipids
Bacteria contain a variety of immune stimulating glycolipids in their cell wall and an objective of the research group is to understand how these glycolipids can either enhance or help treat disease. Specific research interests include the role of trehalose glycolipids in the pathogensis of M. tuberculosis, and how the same glycolipids, and others such as lipoteichoic acid (LTAs), can be used as vaccine adjuvants. We are also interested in identifying novel glycolipids from good ‘gut’ bacteria, such as bifidobacteria, and in determining how these molecules influence the immune response.
A protecting-group-free approach to drug design
The use of protecting groups in synthesis has become the norm over the last century, and many chemists accept them without question. Protecting-groups are useful: they assist in controlling the chemo- and regio-selectivity of reactions, and they have allowed for the synthesis of remarkably complex molecules for a long time.
The disadvantage of protecting groups is that they require organic solvents for reaction, workup and purification which has detrimental to the environment. Extensive protecting group manipulations also lead to lengthy syntheses requiring both a protection and deprotection step per protecting group, resulting in reduced atom economy and reaction efficiency.
Our research group is interested in developing organic reaction that allow for the protecting-group-free total synthesis of biologically important molecules. Representative reactions include a PGF-Vasella reductive amination and an I2-mediated carbamate annulation, which have been used en route to the synthesis of azasugars and other small molecule drugs.
Glycolipids play an important role in many biological processes and we are interested in developing a variety of “chemical tools” that allows for the study of glycolipids in vitro and in vivo. Examples include the use of Affinity based proteome profiling (AfBPP), fluorescent probes, and systematically modifying glycolipids core to determine structure-activity relationships (SARs). In this way, our research group has developed a-galactosyl-ceramide (a-GalCer) and isoglobotrihexosylceramide (iGb3) probes to better understand how to exploit the anti-cancer potential of these molecules. The group has also developed trehalose glycolipid probes to investigate how the receptor Mincle influences the binding and uptake of these glycolipids.
The following research projects are now available:
- Glycolipid adjuvants for anti-cancer immunotherapy
- Green approach to anti-tuberculosis drugs
- A sweet solution to asthma
Interested students should contact: