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Research interests
The primary focus of the Mackay group is to understand protein function at the molecular level, with a particular emphasis on two areas:
The molecular mechanisms underlying the control of gene expression and the use of cutting-edge library display technology for the design of new proteins and peptides with tailored functions.
Experimental approaches range from molecular and cell biology and biochemistry through to biophysical methods. High-quality physical infrastructure is available to support this work, including NMR spectrometers (600 and 800 MHz with cryosystems), X-ray crystallography, CD, analytical ultracentrifugation, Biacore, IT/DSC instruments, Nanotemper microscale thermophoresis, multi-angle laser light scattering, mass spectrometry and cell culture and fermentation facilities.
Prof. Mackay has active collaborations with researchers in Germany, New Zealand, the USA and the United Kingdom.
Major findings include:
(a) The first demonstration that zinc fingers found in transcription factors (TFs) act as protein-recognition domains. ZFs are the most common protein domain in higher eukaryotes and are used extensively in nature in the regulation of gene expression. Since their discovery, these domains were held to be nucleic-acid-binding motifs. However, in a review in the leading journal TiBS, he and Merlin Crossley postulated that ZF domains can also function as protein interaction motifs, dramatically broadening their functional scope and having profound implications for genome annotation and protein function prediction. Their subsequent work provided experimental verification of this hypothesis in >20 articles.
(b) Elucidation of the mechanism for recruitment of GATA1 by the bromodomains protein BRD3. In collaboration with Gerd Blobel (USA), he established that the recruitment of the transcription factor GATA1 to its target loci is dependent on lysine acetylation within GATA1 and recognition by the epigenetic regulatory protein BRD3. He went on to determine the structural basis for this phenomenon . These were some of the first data to provide a mechanistic understanding of the mechanisms by which post-translational modifications of TFs can regulate their activity in a manner similar to that demonstrated by histones.
(c) Discovery of the mechanism by which alpha-globin is chaperoned during haemoglobin assembly. A chaperone for the inherently unstable alpha-chain of haemoglobin had been postulated for decades. He worked with Mitch Weiss (St Judes) to characterize the function, structure and biochemistry of the alpha-globin chaperone AHSP. This work (published in Nature and Cell) provided significant insight into causes of beta-thalassemia and sickle cell anemia.
The primary focus of the Mackay group is to understand protein function at the molecular level, with a particular emphasis on two areas:
The molecular mechanisms underlying the control of gene expression and the use of cutting-edge library display technology for the design of new proteins and peptides with tailored functions.
Experimental approaches range from molecular and cell biology and biochemistry through to biophysical methods. High-quality physical infrastructure is available to support this work, including NMR spectrometers (600 and 800 MHz with cryosystems), X-ray crystallography, CD, analytical ultracentrifugation, Biacore, IT/DSC instruments, Nanotemper microscale thermophoresis, multi-angle laser light scattering, mass spectrometry and cell culture and fermentation facilities.
Prof. Mackay has active collaborations with researchers in Germany, New Zealand, the USA and the United Kingdom.
Major findings include:
(a) The first demonstration that zinc fingers found in transcription factors (TFs) act as protein-recognition domains. ZFs are the most common protein domain in higher eukaryotes and are used extensively in nature in the regulation of gene expression. Since their discovery, these domains were held to be nucleic-acid-binding motifs. However, in a review in the leading journal TiBS, he and Merlin Crossley postulated that ZF domains can also function as protein interaction motifs, dramatically broadening their functional scope and having profound implications for genome annotation and protein function prediction. Their subsequent work provided experimental verification of this hypothesis in >20 articles.
(b) Elucidation of the mechanism for recruitment of GATA1 by the bromodomains protein BRD3. In collaboration with Gerd Blobel (USA), he established that the recruitment of the transcription factor GATA1 to its target loci is dependent on lysine acetylation within GATA1 and recognition by the epigenetic regulatory protein BRD3. He went on to determine the structural basis for this phenomenon . These were some of the first data to provide a mechanistic understanding of the mechanisms by which post-translational modifications of TFs can regulate their activity in a manner similar to that demonstrated by histones.
(c) Discovery of the mechanism by which alpha-globin is chaperoned during haemoglobin assembly. A chaperone for the inherently unstable alpha-chain of haemoglobin had been postulated for decades. He worked with Mitch Weiss (St Judes) to characterize the function, structure and biochemistry of the alpha-globin chaperone AHSP. This work (published in Nature and Cell) provided significant insight into causes of beta-thalassemia and sickle cell anemia.
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Sile F. Yang, Christopher B. Nelson, Jadon K. Wells, Madushan Fernando,Robert Lu, Joshua A. M. Allen, Lisa Malloy,Noa Lamm, Vincent J. Murphy,Joel P. Mackay, Andrew J. Deans,Anthony J. Cesare,
Nature Communicationsno. 1 (2024): 1-15
Vignesh Rajendiran,Nivedhitha Devaraju,Mahdi Haddad,Nithin Sam Ravi, Lokesh Panigrahi,Joshua Paul, Chandrasekar Gopalakrishnan,Stacia Wyman, Keerthiga Ariudainambi,Gokulnath Mahalingam,Yogapriya Periyasami,Kirti Prasad,
Molecular therapy : the journal of the American Society of Gene Therapyno. 3 (2024): 663-677
ACS CHEMICAL BIOLOGYno. 1 (2023): 141-152
Jason K. K. Low,Karishma Patel,Natasha Jones,Paul Solomon,Alexander Norman, Joshua W. C. Maxwell, Petr Pachl, Jacqueline M. Matthews,Richard J. Payne,Toby Passioura,Hiroaki Suga,Louise J. Walport,
Elizabeth A. Werren, Alba Guxholli,Natasha Jones,Matias Wagner,Iris Hannibal,Jorge L. Granadillo,Amanda V. Tyndall,Amanda Moccia, Ryan Kuehl, Kristin M. Levandoski, Debra L. Day-Salvatore,Marsha Wheeler,
Human Genetics and Genomics Advancesno. 3 (2023): 100198-100198
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