Michael Wheatcroft

This role involved managing the Avipep Research team responsible for the production Avibody proteins and their conjugation to cytotoxic molecules for development of therapeutic candidates for cancer therapy. Avibody proteins represent a novel antibody fragment format with superior characteristics over traditional antibodies for the development of antibody drug conjugates. In addition, Avipep has developed a novel 'loading' technology for specific, quantifiable loading of cytotoxic drugs and/or PEG molecules to optimise the desired clinical characteristics; namely tune-able pharmacokinetics and efficient tumour-loading resulting in some very exciting ADC candidates for cancer therapy. www.avipep.com.au

Avipep is the lead company in a consortium of Biologic cancer-drug development institutions, companies & organisations based in (but not limited to) the state of Victoria, Australia. The consortium draws together a number of organisations representing a full spectrum of preclinical and clinical specialities to underpin the development of Avipep's first clinical candidate; PEG-AVP0458 in prostate and ovarian cancer. Concurrent with my duties as Research Manager at Avipep, I managed the preclinical development of Avipep's lead candidate; PEG-AVP0458 (an Avibody protein modified with PEG to achieve optimal pharmacokinetics & tumour-targetting) for a first-time-in-man clinical study in prostate and ovarian cancer.

This position concerned the production and characterisation of recombinantly-expressed antigens and antibodies for use in phage display selections. > All steps in the production of purified proteins; molecular biology/cloning, expression in mammalian or baculovirus cells & purification to homogeneity (e.g. IMAC, ProteinA/G, ion exchange & gel filtration). > Performed characterisation of proteins & peptides using a panel of biophysical techniques for validation e.g. mass spectrometry (MALDI-ToF), size exclusion & reverse phase chromatography by HPLC, SDS-PAGE, Light Scattering (MALS), Western blots & concentration determination. > Carried out lead isolation & optimisation campaigns using phage display to select recombinant antibody clones binding to protein and peptide targets. > Principal specialist on the site for the analysis of protein:protein interactions by surface plasmon resonance (BIAcore & ProteOn), kinetic exclusion (Kinexa), cell-based assays (FMAT) and immunological assays (ELISA). > Assisted in writing Quality-system documents to implement GLP policy. > Interpreting and reporting protein assay results to multi-disciplinary project teams in regular progress meetings and at departmental presentations.

Providing research assistance to a large academic group primarily by expressing and purifying recombinant multi-domain proteins. > Expression of proteins in E. coli & Streptomycetes from shake-flask to fermenter (20L) scale. > Purification of native & His-tagged proteins to homogeneity by chromatography using IMAC, salt precipitation, Ion exchange, Hydrophobic interaction, Gel filtration etc. > Characterisation of proteins & protein:protein binding e.g. size exclusion, analytical ultracentrifugation and mass spectrometry (ESI LC/MS). > Maintenance of lab instruments & tuition of colleagues in the use of stirred-tank fermenters, HPLC, FPLCs, chromatography columns etc. > Administrating laboratory policies and implementing Health & Safety guidelines.

A member of the antibody high-throughput screening team, I was involved in the identification of candidate therapeutic antibodies from phage display selections. > Performed high-throughput assays using colorimetric & radio-isotope based techniques. > Carried out cell culture for in vivo assays measuring binding of proteins to mammalian cells.

This company dealt exclusively with the dispensing of cytotoxic pharmaceuticals for chemotherapy applications in hospitals all over Australia. > I was involved in all stages of preparation of the final product, including dispensing in a sterile room, confirming dosage calculations and despatch. > Adherence to strict regulatory pharmacy guidelines.

Under the guidance of Professor Peter Leadlay, I studied the substrate specificity of polyketide synthases, a class of enzymes involved in the biosynthesis of a variety of natural products, using a wide range of proteomic techniques including: > Standard molecular biological techniques (PCR, DNA extraction, cloning etc) to develop a range of expression & cloning vectors. > Optimisation of protein expression in E. coli and Streptomycete hosts and subsequent purification to homogeneity to maximise yields for assays & structural studies. > Characterisation of proteins and their binding interactions by mass spectrometry (ESI-MS), analytical ultracentrifugation; Western blotting. > Development and validation of a novel, HPLC-based, kinetic assay. > Structure-function analysis of proteins by site-directed mutagenesis, crystallisation trials and homology modelling.

The course primarily involved modules in microbiology, biochemistry and molecular biology as well as the study of micro-organisms and their industrial applications. My honours research project investigated the structure:function relationships of DNA methylating enzymes using in vitro assays. > Molecular biology-based DNA methylation assays. > Protein purification & in vitro assays to study the activity of a panel of mutants.