Monday, 14 October 2024 4:00pm – 5:00pm

This seminar will be delivered in Lecture Theatre 2

Speaker: Dr Miaomiao Liu

Host: Dr Johnny Liu

Title: Drug Discovery Using Native MS: Protein-Ligand Complexes and Beyond

Abstract: Native mass spectrometry (native MS) relies on non-denaturing electrospray- ionization (ESI) to recognize multi-charged proteins in their near-native states. It is a label-free, fast, and accurate method that permits the direct observation of non-covalent and covalent protein-ligand complexes. Over the last 5 years, we have advanced the application of native from measuring binding interactions of individual small molecules (ligands) with proteins, to screening libraries of compounds and compound mixtures, to protein mixtures, and ternary protein-ligand-protein molecular glue type complexes. Our outcomes which involved collaborations with disease experts in academia and industry include identification of new cancer, malaria, neurodegenerative diseases, tuberculosis and COVID-19 therapeutic candidates.

The current focus lies on further refining our platform to probe increasingly complex mixtures of proteins using known small molecule drugs and bioactive compounds identified from phenotypic assays where the target protein is unknown. The ultimate aim is to precisely and directly identify the target protein for every small molecule drug candidate within disease-relevant cell lysates. This ongoing development holds immense promise for advancing drug discovery and understanding disease mechanisms.

Bio: Dr Miaomiao Liu is an NHMRC Emerging Leadership Fellow and an ECR Research Leader at the Institute for Biomedicine and Glycomics. She obtained a joint PhD degree in 2017 from Griffith University and the University of Chinese Academy of Sciences. She has a career total of 52 research outputs including 49 peer- reviewed publications ,1 book chapter and 2 patent applications in the field of native MS, natural product chemistry and metabolomics. Dr Liu has attracted >$4.15M in research funding ($1.34 M as CIA and $1.2M as CIB) including two fellowships (NHMRC EL1 Investigator Fellowship (2024- 2028); Japan Society for the Promotion of Science (JSPS) Fellowship, 2022-2023) and a commercial project with big pharma industry partner Genentech (CIB, 2019 – 2021).

Her multidisciplinary research program rests on three pillars:

1. Target identification by native mass spectrometry to identify the molecular target of bioactive molecules without the need to derivatise the molecule.

2. Characterising of ternary complex formed between a target protein, a PROteolysis Targeting Chimera (PROTAC) and an E3-ubqiutin ligase by native mass spectrometry.

3. Natural products chemistry by combining phenotypic-based drug discovery and target-based drug discovery to identify active compounds from natural resources.