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Biography

Understanding the role of nutrition and the gut microbiome in physiology

Eminent immunologist Professor Charles Mackay is exploring an exciting new concept- that nutrition and the gut microbiome have profound influences on physiology, particularly immune responses (see Maslowski and Mackay, Nature Immunology 2009 and Thorburn, Macia and Mackay, Immunity 2014). Charles Mackay demonstrated that dietary fibre and its breakdown fermented products, the short chain fatty acids (SCFAs) influence gut homeostasis, the composition of the gut microbiota, immune tolerance, and inflammatory responses. His research focuses on cellular and molecular pathways, such as the 'metabolite-sensing GPCRs, and epigenetic pathways including HDAC inhibition.

Charles Mackay believes there is considerable potential to manipulate immune responses using 'medicinal foods', as well as novel gut microbial species. He is developing new diets that release very high amounts of beneficial SCFAs in the gastrointestinal tract.  

'This is an exciting area for us. People perhaps haven't totally appreciated how connected these major systems are. They influence one another. The microbes that colonise our intestinal tract are a part of this mix. Understanding how diet and the metabolism of dietary substances affect gut microbes and how they affect our immune system is a brand new direction in medical research.'

He says immunologists in the past did not give much credence to prebiotics (beneficial foodstuffs) and probiotics (beneficial microbes) as affecting immune function and inflammatory diseases. These concepts were regarded as being on the fringe of acceptable science. 'That's partly because scientists like to see the molecular mechanisms before they will fully accept new ideas. If you have a phenomenon or an observation and can couple that with a molecule or gene, then you can see the entire picture.'

Metabolite-sensing GPCRs
The interaction between the body's immune and metabolic systems is another major area of research that Charles is leading at Clayton. Charles is a leader in the field of 'metabolite-sensing GPCRs, receptors that play dual roles in immune responses and metabolism. Charles published on the relevance of the main receptor characterised to date, GPR43 (Maslowski et al Nature 2009). His main interest currently is GPR65, which he believes is fundamental for barrier homeostasis (gut, skin and lung). 

Charles believes that the incidence of diabetes, cardiovascular disease, allergies and asthma, and auto-immune diseases in Western countries relate to a changing diet. Reduced fibre and fish, increased processed foods and resulting obesity has altered the mix of microbes and the things they produce. All this changes our immune system, gut homeostasis and the regulation of inflammatory responses. 

Leukocyte trafficking through the body

Charles has received international recognition for major breakthroughs in understanding the role of white blood cells and how they move around the body (see review, Von Andrian and Mackay, NEJM 2000). This work has also led to new understanding on how Human Immunodeficiency Virus (HIV) infects cells. His more recent research into leukocyte traffic to inflamed tissues has resulted in the development of a new antibody treatment (anti-C5aR), now in human clinical trials. Charles is an expert on chemokines and their receptors and is exploring the biological roles of receptors such as CXCR7, CCR6 and CXCR3. 




Keywords

  • T-cell migration
  • GPCR biology
  • nutrition and immunology
  • gut microbiota

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Projects 2009 2020

Research Output 2000 2017

A fully humanized IgG-like bispecific antibody for effective dual targeting of CXCR3 and CCR6

Robert, R., Juglair, L., Lim, E. X., Ang, C., Wang, C. J. H., Ebert, G., Dolezal, O. & Mackay, C. R. 1 Sep 2017 In : PLoS ONE. 12, 9, e0184278

Research output: Research - peer-reviewArticle

c-Myb Regulates the T-Bet-Dependent Differentiation Program in B Cells to Coordinate Antibody Responses

Piovesan, D., Tempany, J., Di Pietro, A., Baas, I., Yiannis, C., O'Donnell, K., Chen, Y., Peperzak, V., Belz, G. T., Mackay, C. R., Smyth, G. K., Groom, J. R., Tarlinton, D. M. & Good-Jacobson, K. L. 18 Apr 2017 In : Cell Reports. 19, 3, p. 461-470 10 p.

Research output: Research - peer-reviewArticle

Open Access
File

Gut microbial metabolites limit the frequency of autoimmune T cells and protect against type 1 diabetes

Marino, E. , Richards, J. L. , McLeod, K. H. , Stanley, D. , Yap, Y. A. , Knight, J. , McKenzie, C. , Kranich, J. , Oliveira, A. C. , Rossello, F. J. , Krishnamurthy, B. , Nefzger, C. M. , Macia, L. , Thorburn, A. , Baxter, A. G. , Morahan, G. , Wong, L. H. , Polo, J. M. , Moore, R. J. , Lockett, T. J. & 4 others Clarke, J. M., Topping, D. L., Harrison, L. C. & Mackay, C. R. May 2017 In : Nature Immunology. 18, 5, p. 552-562 13 p.

Research output: Research - peer-reviewArticle

Metabolite-sensing G protein-coupled receptors-facilitators of diet-related immune regulation

Tan, J. K., McKenzie, C., Mariño, E., Macia, L. & Mackay, C. R. 26 Apr 2017 In : Annual Review of Immunology. 35, p. 371-402 32 p.

Research output: Research - peer-reviewReview Article