Associate Professor David Ackerley
PhD University of Otago | BSc (Hons) University of Otago
I am a microbiologist and enzyme engineer, with a primary focus on discovery, characterisation, engineering and application of useful bacterial enzymes, and of novel antibiotics to counter the spread of multi-drug resistant bacteria. My particular speciality is in tailoring enzyme activities by directed evolution - a powerful approach for enzyme engineering that applies Darwinian evolutionary principles at a single-gene level, using iterative rounds of focused mutagenesis followed by artificial selection of enhanced variants to improve desirable activities. One of the coolest things about that approach is that if you have designed your system sufficiently well, you don’t necessarily need to understand how your enzyme works to achieve some very useful outcomes, which can in turn shed light on key mechanistic details. One of the less cool things is that, as with Aladdin’s genie, you need to be very precise about what you wish for – if things can go wrong, they probably will! But they say we learn more from our mistakes than our successes, so there’s that.
Other than research, my main role at VUW is as the Biotechnology Programme Director. I have played a primary role in designing and running the programme since its inception in 2006, and am the main course lecturer for BTEC101 and BTEC201. Biotechnology at VUW is a “science first” course that emphasises problem solving inmolecular biology, and the impact of the solutions on society. The VUW Biotechnology Programme is particularly strong in areas of Microbial Biotechnology, Reproductive Biotechnology, and Drug Discovery.
A major theme of my research is directed evolution, artificial acceleration of rates of mutation and recombination in genes and genomes, and selection of variants with improved qualities.
My lab group employs these techniques both to improve specific functions of enzymes and bacteria, and to study their physiology. In particular, we are developing:
1. Improved bacterial nitroreductase enzymes for activation of chemotherapeutic prodrugs and imaging molecules
2. Domain-shuffled non-ribosomal peptide synthetase enzymes that synthesise novel secondary metabolites
3. Highly specific phosphopantetheinyl transferases that can tether molecular linkers to specific peptide “tags”
4. DNA ligases that have been evolved for improved blunt-end fragment joining.
We also have a strong interest in metagenomic biodiscovery of valuable enzymes and drugs from the unculturable bacterial communities present in diverse environmental samples.
JN Copp, AM Mowday, EM Williams, CP Guise, A Ashoorzadeh, AV Sharrock, JU Flanagan, JB Smaill, AV Patterson, DF Ackerley. 2017. Engineering a multifunctional nitroreductase for improved activation of prodrugs and PET probes for cancer gene therapy. Cell Chemical Biology 24: 391–403.
AS Brown, KJ Robins, DF Ackerley. 2017. A sensitive single-enzyme assay system using the non-ribosomal peptide synthetase BpsA for measurement of L-glutamine in biological samples. Scientific Reports 7: 41745.
JG Owen, MJ Calcott, KJ Robins, DF Ackerley. 2016. Generating functional recombinant NRPS enzymes in the laboratory setting via peptidyl carrier protein engineering. Cell Chemical Biology 23: 1395-1406.
AM Mowday, A Ashoorzadeh, EM Williams, JN Copp, S Silva, MR Bull, M Abbattista, RF Anderson, JU Flanagan, CP Guise, DF Ackerley, JB Smaill, AV Patterson. 2016. Rational design of an AKR1C3-resistant analog of PR-104 for enzyme-prodrug therapy. Biochemical Pharmacology 116: 176-187.
DF Ackerley. 2016. Cracking the Nonribosomal Code. Cell Chemical Biology 23: 535-537.
WO/2016/080846: “Salicylamide antibiotics”. Inventors: DF Ackerley and JN Copp. Published 26 May, 2016.
WO/2015/084189: “Methods of detecting and measuring glutamine and analogues thereof, and methods related thereto”. Inventors: DF Ackerley, AS Brown and KJ Robins. Published 11 June, 2015.
WO/2014/031012: “Novel prodrugs and methods of use thereof”. Inventors: JB Smaill, AV Patterson, A Ashoorzadeh, CP Guise, AM Mowday, DF Ackerley, JN Copp, EM Williams. Published 27 February, 2014.