Seminar Series ECR AND STUDENT HDR SEMINAR

Click here to watch the Seminar

Date: 24th November 2022

Time: 12:30pm

Venue: AIBN Level 1 Seminar room or online via zoom https://uqz.zoom.us/j/webinar/81920361276

We are pleased to present Dr Julio Aguado to speak on Understanding mechanisms of aging in human brain organoids and in vivo.

Abstract
The progressive accumulation of senescent cells in vivo strongly contributes to brain aging and neurodegenerative co-morbidities. We report on the establishment of a novel patient-derived brain organoid model of Ataxia-telangiectasia (A-T), a genetic disorder characterized by chronic inflammation, neurodegeneration and premature entry into cellular senescence (Aguado et al, Ageing Research Reviews 2022). Through transcriptome profiling and gene network analysis, we found multiple pro-inflammatory signatures enriched in human brain organoid (hBO) models of A-T. Mechanistically, we show that cGAS and STING inhibition effectively suppresses self-chromatin-triggered senescence-associated secretory phenotype (SASP) expression in A-T hBOs, inhibits astrocyte senescence and neurodegeneration, and ameliorates A-T brain organoid neuropathology (Aguado et al, Aging Cell 2021). In addition to premature aging disorders, we will also show our unpublished progresses in the characterization of SARS-CoV-2-induced cellular senescence in hBOs, including chromatin changes associated with cellular senescence and DNA damage signalling. Although senolytics – drugs that selectively eliminate senescent cells – alleviate the detrimental effects that arise from these cells, their impact in the aging human brain remains largely uncharacterized. We explore the impact of multiple senolytic interventions on physiologically-aged hBOs as well as hBOs exposed to different variants of SARS-CoV-2. Interestingly, transcriptomic analysis across both experimental conditions and individual senolytic treatments revealed a differential but consistent effect in alleviating the SASP. Finally, senolytic interventions in mice overexpressing human ACE2 – an in vivo model for SARS-CoV-2 neuroinvasion- recapitulated the phenotypes observed in human BOs and further proved increased lifespan and improved the clinical picture of the infected animals. Overall, our results will show the impact of senotherapies in a progeroid genetic background, virus-induced senescence and physiologically-aged models of human brain aging.

Bio

Dr Julio Aguado obtained his PhD in 2018 from the European School of Molecular Medicine (University of Milan) as a Marie Curie fellow of the European Union where he investigated the role of non-coding RNAs generated upon induction of DNA damage. He has published several first-author papers on mechanisms of aging in top-tier journals including Nature Communications, Nature Protocols and Aging Cell. Dr Aguado currently works as a Research Fellow in the Wolvetang group at the Australian Institute for Bioengineering and Nanotechnology (AIBN), where his focus is centered in the study of human aging and its interplay with DNA damage, neurotoxicity and inflammation. His research is supported by grants awarded to Julio Aguado as CIA, including a NHMRC Ideas Grant (APP2001408), a University of Queensland Early Career Researcher Grant (application UQECR2058457), a Brisbane Children's Hospital Foundation grant (Project-50308) and a Jérôme Lejeune Postdoctoral Fellowship (Paris, France).
 

We are pleased to present Lauren Geurds to speak on Nanocellulose-based polymer brush systems as a template for metal nanoparticle synthesis.

Abstract
Conductive hydrogels based on metallic nanoparticles (MNPs) are heavily explored due to their outstanding conductive properties and extensive applications in different industries, including biosensors, flexible electrodes, and optoelectronics. However, the production of well-oriented MNPs in hydrogels is challenging. Due to the high surface area and interaction energy, MNPs tend to aggregate, limiting their ability to be homogeneously dispersed into a polymer, leading to poor electrical conductivity and mechanical properties. Using a one-component system, such as cellulose nanocrystals (CNC) templated polymer brushes for the guided formation of MNPs, could solve current limitations. CNC is the primary building block of plants and gained significant attention as a sustainable and biodegradable material with numerous chemically accessible hydroxyl groups, allowing the stabilization of MNPs and controllable mechanical properties. Here we demonstrate an optimized approach for introducing block-copolymers on the CNC using surface-initiated Atom Transfer Radical Polymerisation (SI-ATRP) and click chemistry. By tuning the polymer brush density and length, templating ability and mechanical properties can be fine-tuned to obtain desired characteristics. Furthermore, understanding how these parameters impact each other will guide the future tailoring of the surface modification and evaluate the potential of CNC-grafted polymer brushes for the guided formation of MNPs as a potential conductive printable ink.

BIO

Lauren Geurds completed her B.Sc. in chemistry at the HAN University of Applied Sciences, The Netherlands. In 2019, she received a second B.Sc. with Honours class I in the field of biochemistry at the University of Queensland, Australia. In January 2020, she started her PhD in the Australian Institute for Bioengineering and Nanotechnology (AIBN) at the University of Queensland under the supervision of Dr Nasim Amiralian, Prof Alan Rowan, and Dr Jan Lauko.