Bio21 Members Funded for Discovery

Scheme Name: Discovery Projects

Lead Investigator: Prof Spencer Williams

DP210100233 — The University of Melbourne

Dissecting a major sulfur cycling pathway: sulfoglycolysis. This project will elucidate the molecular details of sulfoglycolysis, a group of metabolic pathways through which the sulfur-containing sugar sulfoquinovose is catabolized. The project will employ an integrated metabolomic, chemical, biochemical and structural approach to dissect how various sulfoglycolytic organisms degrade sulfoquinovose. This project will deliver a deeper understanding of this major biochemical pathway and develop new chemical and metabolic approaches to manipulate sulfur cycling in the environment. Benefits will include biotechnology applications of newly discovered proteins, and sustainable approaches to reduce our dependence on agricultural fertilisers.

Scheme Name: Discovery Projects

Lead Investigator: Prof Spencer Williams

DP210100235 — The University of Melbourne

Control of immune recognition and response by microbial metabolites. This project aims to study immune recognition of microbial metabolites and develop reagents to control immune responses. Chemical synthesis will be used to develop new antigens for unconventional T cells and the first soluble agonists and antagonists of a glycolipid-sensing immune receptor. Expected outcomes include the discovery of new immune effectors, broadening our knowledge of the repertoire of small molecules that can be sensed by the immune system, and developing chemical approaches to promote or dampen immune responses. Major benefits include research training in chemical biology, strengthened international linkages and fundamental insights into the chemical basis of immune recognition and response.

Scheme Name: Discovery Projects

Lead Investigator: Dr Elizabeth Hinde

DP210102984 — The University of Melbourne

The role of HP1 alpha dimerisation in maintaining chromatin structure. Heterochromatin protein 1 alpha (HP1a) is an architectural protein that decorates three-dimensional genome organisation and through self-association into HP1a dimers regulates global gene expression. While there is extensive biochemical evidence on how HP1a molecules bind DNA, dimerise and bridge nucleosomes close together, we still do not know how HP1a regulates higher order chromatin structure in the context of a living cell. Thus, by use of cutting-edge fluorescence microscopy methods, the overall aim of this research project is to determine the biophysical mechanism by which the HP1a monomer to dimer transition spatially and temporally modulates live cell chromatin network organisation to ensure faithful transmission of the genome.

Scheme Name: Discovery Projects

Lead Investigator: Prof Paul Gooley

DP210100998 — The University of Melbourne

Uncovering mechanisms of protein multifunctionality. This project aims to use viral proteins to uncover fundamental mechanisms underlying protein multifunctionality, a central but poorly understood aspect of biology. This project expects to use multidisciplinary approaches to define novel and unexpected mechanisms by which single protein sequences can generate proteins with profoundly different structures and functions. Expected outcomes include a major shift in the understanding of protein function in life, with most immediate impact in virology. This should provide significant benefits in identifying new strategies for treating viral infections, but also enhance developing multidisciplinary approaches to solve complex biological problems.

Dr Francesca Cavalieri; Dr Marc-Antoine Sani; Dr Christina Cortez-Jugo; Associate Professor Nitin Mantri

Bioprogramming the behaviour of nanoparticles in live cells by nanoscopy. The project aims to develop safer materials that are sustainably sourced from sweet corn, and investigate using advanced imaging technologies, how these materials are processed in biological systems, including human and plant cells. This project expects to generate new knowledge in the optimal design of materials that can be used safely and effectively in biological applications in medicine and in agriculture. Expected outcomes of this multidisciplinary project include a library of highly biocompatible nanomaterials and expanded knowledge on imaging technologies and structure-function relationship of nanomaterials in biological cells. This should provide significant benefits, such as improved crop yields and safer transfection agents.

Associate Professor Christopher Walsh; Dr Yung En Chee; Dr Rhys Coleman; Professor Ary Hoffmann

Linkage Projects

Lead Investigator:

A/Prof Christopher Walsh

LP200100381

Improving stream management using ecological modelling and DNA barcodes. Rivers and streams provide invaluable ecosystem services, yet are commonly degraded by human activities: a problem likely to be exacerbated by thermal and flow regimes being altered by climate change. Stream biodiversity is both a value and an indicator of ecological health: effective stream management requires prediction of biodiversity responses to natural environmental and human-impact gradients. By compiling a dataset of macroinvertebrate species using new DNA metabarcoding, modelling their distributions, and ranking biodiversity by reach, we will develop molecular and quantitative spatial tools to provide data-driven, landscape-scale decision support for protecting and restoring streams: an urgent need for stream managers globally.