Ian Macreadie, Ph D

JAD profile

Affiliation(s): 

RMIT University; Edith Cowan University

Areas of Interest: 

Yeast as a model for Alzheimer's disease

Biography & Research: 

Ian Macreadie obtained his Ph.D. in yeast genetics and molecular biology at Monash University in the labs of AW Linnane and HB Lukins. This was followed by a Post-Doc at University of Texas Health Science Center at Dallas with Ron Butow. He played key roles in identifying the structure and functions of mitochondrial genes encoding three ATPase subunits, the ribosomal protein var1, and an endonuclease encoded within a mitochondrial intron. The endonuclease cleaved the intron lacking sequences, to bring about gene conversion. In 1985 he commenced a 24 year career at CSIRO, Division of Protein Chemistry, Parkville. At CSIRO he developed highly versatile novel yeast expression systems (pYEX vectors) that were marketed internationally by companies including AMRAD and CLONTECH. Macreadie’s first project at CSIRO was led by Ahmed Azad and was one of the first projects funded by the National Biotechnology Program. The project aimed to produce a sub-unit vaccine for Infectious Bursal Disease Virus, a major disease of poultry, and it was inspired by the success of the Hepatitis B vaccine. The yeast expression systems enabled production of a successful vaccine, the world’s second viral subunit vaccine. From 1990-2000 he was seconded to the Biomolecular Research Institute, led by Peter Colman. Macreadie continued to use the yeast expression systems and employed them for the study of HIV (AIDS) proteins Vpr, Nef, Vpu and Vif. The Vpr protein caused a cell growth arrest in yeast cells, a phenomenon that also occurred in infected lymphocytes. They were also used for the identification of inhibitors of Nef and Vpr. Later at the Biomolecular Research Institute he focused on sulfa drug resistance and took a particular interest in the folate synthesis pathway which are the targets of the oldest chemically-synthesised drugs, the sulfa drugs. With Peter Iliades he reverse-engineered yeast to show that DHPS mutations associated with sulfa drugs in the AIDS associated pathogen, Pneumocystis jirovecii (which was unculturable), did indeed cause drug resistance in yeast. These sulfa drugs are text book examples of competitive inhibitors of pABA, but with Onisha Patel he showed that they could be conjugated, in the place of pABA, to form sulfa-dihydropteroate, and to inhibit DHFR as well. With Mike Lawrence and James Swarbrick he went on to screen for new antifolates for malaria and Pneumocystis based on structural studies of DHPS and HPPK. Most recently he has focused on development of a yeast model for Alzheimer’s Disease to aid in the understanding of chemopreventatives for Alzheimer’s disease. The yeast being studied have been engineered to produce amyloid beta in native form and as GFP fusion proteins. Their use enables studies of compounds that are known to reduce the incidence of Alzheimer’s Disease, as well as novel compounds. Currently, at RMIT University he coordinates courses on Industrial Microbiology and Protein Technologies, while continuing research on chemoprevention of Alzheimer’s disease, exploitation of microbes for their commercial benefits and understanding the requirements that enable successful microbial culture as well as their preservation. He is author of 140 research publications and six patents. His awards include a 1990 Fulbright Senior Scholar Award, 1996 Frank Fenner Research Award, 1997 CSIRO Chairman's Medal (a team award), 1998 Ramaciotti Travel Award, 2002 Brailsford Robertson Research Award (with Dennis Taylor), 2004 EMBO Short Term Fellowship, 2005 Merck, Sharp and Dohme Mycology Award, 3rd place in Bioscience Technology’s Researcher of the Year Award in 2009. He was National Secretary of the Australian Society for Biochemistry and Molecular Biology from 1997-2000, and is Editor of Microbiology Australia (since 2006). He was Chair of the Organising Committees for the 23rd International Conference on Yeast Genetics and Molecular Biology (2007) and the 11th International Symposium on the Genetics of Industrial Microorganisms (2010).