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Mathias Lab research

CollaborationsStudent research projects | Publications

About Dr Rommel Mathias

Dr Mathias completed a Bachelor of Biomedical Science with Honours at Melbourne University. Under the supervision of Prof Richard Simpson, he studied epithelial-mesenchymal transition as a process facilitating cancer metastasis, and received his PhD in 2009.

In 2012, he was awarded a NHMRC CJ Martin Early Career Fellowship for Postdoctoral studies at Princeton University. In the laboratory of Prof Ileana Cristea, he discovered mitochondrial SIRT4 as the first mammalian cellular lipoamidase, with its enzymatic activity inhibiting pyruvate dehydrogenase (Cell, 2014).

Dr Mathias returned to the La Trobe Institute for Molecular Science in late 2014, for the Australian-based component of his fellowship. In 2015, he was awarded a NHMRC Project Grant as a New Investigator to investigate the viral pathogenesis of HCMV infection. In 2016, Dr Mathias moved to Monash University, in a joint appointment between the Department of Microbiology, and the Department of Biochemistry and Molecular Biology. He heads the ‘Molecular Systems Virology' research group.


Our research

Current projects

HCMV infection is the leading cause of congenital birth defects, causing permanent hearing loss, vision impairment, and mental retardation. In immuno-competent individuals, primary HCMV infection is usually cleared without complication. However, the virus remains latent, and can periodically reactivate causing significant morbidity and mortality in immuno-compromised individuals, such as organ transplant recipients. No vaccine exists despite being previously assigned as the top priority for vaccine development by the U.S. Institute of Medicine, and the discovery of new antivirals is urgently required.

Rather than coding for all egress proteins, viruses have evolved elegant mechanisms to hijack specific host proteins and pathways. Given the dynamic nature of this interplay, research in our laboratory comprehensively investigates egress from both host and viral perspectives, to reveal the essential molecular modulators of the system. Specific projects include:

1. Biogenesis of the HCMV viral assembly complex

2. Hijacking of host exosome pathways by HCMV

Visit Dr Mathias' Monash research profile to see a full listing of current projects.

Research activities

1. Biogenesis of the HCMV viral assembly complex

HCMV is a large double-stranded DNA virus whose 236 kbp genome is known to code for at least 150 proteins. The HCMV virion comprises a nucleocapsid that houses the DNA genome, and is surrounded by a proteinaceous tegument layer, and glycoprotein-containing lipid envelope. During infection, exactly how the virion is assembled and released (egress) remains unknown. However, infection causes extensive organelle remodeling in infected host cells, and produces a structure known as the viral assembly complex (vAC). It is currently thought that the vAC facilitates virion assembly and maturation.

We use a library of mutant viruses that each contain a transposon insertion to disrupt individual genes in the HCMV genome. We use these mutant viruses to identify the essential viral proteins needed to generate the vAC, and critical regulators that enable release of the virion. Using a confocal microscopy-based assay, we screen for defects in Golgi ring, endosome clustering, and secondary envelopment of the virion. This research has identified several viral proteins, that when deleted, block late stages of the viral life cycle. Excitingly, many of these are novel viral proteins with uncharacterized functions, and await further investigation.

2. Hijacking of host exosome pathways by HCMV

HCMV is master at manipulating existing host pathways to benefit completion of the life cycle. It is known that maturing nucleocapsids bud into host membrane-derived structures to acquire the outer virion envelope. However, the origin of the membrane is unknown, and the precise molecular mechanisms remain elusive.

Exosomes are small nanovesicles (50-200 nm) secreted by almost all cell types under normal conditions. We have discovered that during HCMV infection, a subset of viral proteins are exported in host exosomes. Simultaneously, host exosome proteins are incorporated into the HCMV virion. We are currently pinpointing how these processes intersect, and defining how the host pathway is hijacked for viral egress.

Techniques/expertise

Research in our laboratory uses a multidisciplinary approach to better understand host defence mechanisms, and identify cellular pathways that are hijacked by HCMV. We work at the interface between cell biology, virology and quantitative proteomics, and have engineered viruses and reagents to make unique discoveries. All projects have an opportunity to learn standard (tissue culture, western blotting, immune-precipitation, confocal microscopy, RNAi, CRISPR) and advanced (liquid chromatography, mass spectrometry, bioinformatics, electron microscopy) laboratory techniques and skills.

Disease models

HCMV infection of fibroblasts, endothelial and epithelial cells.


Collaborations

We collaborate with many scientists and research organisations around the world. Click on the map to see the details for each of these collaborators (dive into specific publications and outputs by clicking on the dots).


Student research projects

The Mathias Lab offers a variety of Honours, Masters and PhD projects for students interested in joining our group. There are also a number of short term research opportunities available.

Please visit Supervisor Connect to explore the projects currently available in our Lab.