Professor Peter Mace

Research

Our research investigates how protein interactions control development, metabolism, and signalling in humans and plants. We have a particular interest in how regulated proteolysis and kinase signalling can be harnessed for biotechnology and medicine. By integrating discovery biology with cutting-edge protein engineering, our research advances understanding of how cells adapt to their environment and provides new technologies for health and agriculture.

Ubiquitin ligases and kinases in immune and metabolic signalling

The COP1 ubiquitin ligase is a critical regulator of transcription factors in immune and metabolic signalling. COP1 enables ubiquitin-mediated degradation of transcription factors either alone or as part of a larger ubiquitin ligase complex, and recruits substrates directly or with a network of pseudokinase substrate adaptors (Tribbles). We have contributed several key insights into COP1-mediated substrate recruitment and mechanism (Burgess et al., Science Advances 2025; Jamieson et al., Structure 2022; Jamieson et al., Science Signaling 2018). We are continuing to investigate regulation and small molecules that control COP1 and its substrate adaptors as potential therapeutics for metabolic diseases, immune modulation and myeloid cancers.

Synthetic proteins for biodiscovery and diagnostics

We use yeast surface display to identify synthetic protein nanobodies as tools for discovery (Davies et al., Nat Comms 2023; Jamieson et al., Structure 2022), and are actively developing computationally designed protein binders with both RFDiffusion and Bindcraft. Our present work focuses on creating synthetic proteins for diagnostics by combining advanced protein design algorithms with high-throughput display technology to generate stable, high-affinity binders. We are also extending these approaches to probe and modulate cellular signalling, opening new opportunities in next-generation diagnostics, therapeutics, and synthetic biology.

Protein degradation in plant development

The ubiquitin-proteasome system is used extensively in plants to control various aspects of growth, development, and environmental responses. We have several active projects investigating how plant physiology is regulated by protein degradation—in particular uncovering various transcriptional regulators are degraded by the ubiquitination to integrate light, temperature, and circadian signals. These insights will explain how plants adapt their growth to environmental cues, with potential applications in crop improvement and climate resilience.

Stress-activated MAP kinase signalling

We have an ongoing interest in Stress Activated MAP kinase signalling. Our biochemical and structural studies of Apoptosis signal-regulating kinase 1 (ASK1) have uncovered several important features that control ASK1 activity (Trevelyan et al., Science Signalling 2020; Weijman et al., PNAS 2017). We also investigate MEKK1, the only known MAP kinase to possess both kinase and ubiquitin ligase function. We have uncovered a previously unidentified tubulin binding domain in MEKK1 (Filipčík et al., PNAS 2020), and continue to investigate integrated regulation of MEKK1 by ubiquitination and phosphorylation.

Our work is supported by generous grants from the Marsden Fund, Health Research Council of New Zealand, Ministry of Business, Innovation and Employment, the University of Otago, and previously by a Rutherford Discovery Fellowship administered by the Royal Society of New Zealand.