What's On at UWA

Suzanne Neville The School of Chemistry, UNSW, Australia RACI Sargeson Lecture: Molecular Switching Framework Materials

Raffaella Demichelis ARC Future Fellow, School of Molecular and Life Science, Curtin University

Mineral/fluid interfaces at the atomic scale: modelling of materials and processes with potential applications in materials science

R is a free and extremely powerful language and software environment for statistical computing, data analysis, and graphics. This course is designed for those who have no experience with R, but have a basic understanding of statistics. Those without this knowledge are encouraged to attend the Introductory Statistics course first.

Enroll at: http://www.cas.maths.uwa.edu.au/courses/rbasics

Jason Harper School of Chemistry, University of NSW

"Towards reaction control using ionic liquids"

Friday 30 November 2018

GPB3: [G01] Simmonds Lecture Theatre - 10 am

Advanced Molecular Microscopy Symposium

Insights into T cell receptor signalling with single molecule localisation microscopy

Abstract: Two waves of DNA methylation reprogramming occur during mammalian embryogenesis; during preimplantation development and during primordial germ cell (PGC) formation. However, it is currently unclear how evolutionarily conserved these processes are. Here we characterize the DNA methylomes of zebrafish PGCs at four developmental stages and identify retention of paternal epigenetic memory, in stark contrast to the process in mammals. Gene expression profiling of zebrafish PGCs at the same developmental stages revealed that the embryonic germline is defined by a small number of markers that display strong developmental stage-specificity and that are independent of DNA methylation-mediated regulation. We identified promoters that are specifically targeted by DNA methylation in somatic and germline tissues during vertebrate embryogenesis and that are frequently misregulated in human cancers. Together, these detailed epigenome and transcriptome maps of the zebrafish germline provide novel insights into vertebrate epigenome reprogramming and enhance our understanding of the relationships between germline fate acquisition and oncogenesis.

Abstract: Crystal structure prediction (CSP) can provide invaluable insight and direction for the discovery and creation of functional materials, and is a prime example of high-throughput, large scale calculations on high performance computing (HPC) systems. This talk will focus on current methods for crystal structure prediction employed in the Day group at the University of Southampton, and their application to the goals of the LRC centre for functional materials design, examining several molecular and their porous (and dense) forms.

Presenter:Debbie Silvester-Dean Curtin University Title:Ionic Liquids as Materials in Electrochemistry Date:Wednesday 12 December 2018 - 12 noon

Donor-Acceptor Cyclopropanes: - Unique Structural Units to Access Carbo and Heterocyclic Compounds

Epigenetic switching and antisense transcription

Regulation and function in non-coding RNAs in cardiovascular disease

2D Gas Sensors with High Sensitivity and Selectivity: Insight from Theoretical Simulations

Adventures in Computational Chemistry

Yeast 2.0 - building the world’s first functional synthetic eukaryotic genome

Jennifer Young (Dual gradient hydrogel systems for mechanobiology applications): The spatial presentation of mechanical information is a key parameter for cell behavior. We have previously developed a method for creating tunable stiffness gradient polyacrylamide hydrogels with values spanning the in vivo physiological and pathological mechanical landscape. Importantly, we created gradients that do not induce durotaxis in human adipose-derived stem cells (hASCs), thereby allowing for the presentation of a continuous range of stiffnesses in a single sample without the confounding effect of differential cell migration. Using these nondurotactic gradient gels, stiffness-dependent hASC morphology, migration, and differentiation were studied, providing high resolution data on stiffness-dependent expression and localization. Expanding upon this work, we are utilizing these gradient hydrogel systems to study cancer cell-ECM interactions. Interactions with the surrounding microenvironment have been shown to positively influence cancer cell survival and invasion by conferring adhesion-based resistance in response to chemotherapeutic drugs, and subsequently driving metastasis into surrounding tissues. In order to study a wide range of ECM environments, we produce dual-gradient systems by fabricating a gradient of ligands on top of our previously described stiffness gradient hydrogels. Ligand gradients are produced by either a gradient photomask to which proteins can be coupled to the substrate via a UV-sensitive crosslinker or by depositing a gradient of gold nanoparticles onto the hydrogel to which thiolated peptides can readily attach. Using these dual gradient hydrogels, we can better understand the interplay of substrate stiffness, ligand type, and ligand spacing in regulating adhesion-conferred chemoprotection in cancer cells. Andrew W. Holle (Under pressure: the role of multidimensional confinement in mechanobiology): As bioengineers systematically move from simple 2D substrates to more complex 3D microenvironments, the role of cellular and nuclear volume adaptation in response to these substrates is becoming more appreciated. Long, narrow PDMS microchannels, which recapitulate porous extracellular matrix (ECM) networks found in vivo, confine cells to a single axis of migration and require them to utilize a complex synergy of traction force, mechanosensitive feedback, and subsequent cytoskeletal rearrangement. This process exhibits characteristics of the poorly understood mesenchymal-to-amoeboid transition, in which cells alter their migratory phenotype in order to traverse narrow constrictions and more successfully metastasize. During channel permeation, the volume of the nucleus changes, suggesting that nuclear reorganization and volume adaptation is a key step for successful permeation. Volume adaptation is also an important phenomena in stem cell mechanobiology. 3D GelMA hydrogel scaffolds with linear stiffness gradients were used to confine stem cells in three dimensions, with cells in the soft end more able to deform the matrix and increase their cell volume, while those on the stiff end were more confined. Cells on the soft end, which were able to adapt their volume more efficiently, exhibited markers for osteogenesis, while those on the stiff end became more adipogenic. This trend, which is opposite to what is observed on 2D hydrogels, suggests that volume adaptation, not stiffness, is sufficient for mechanosensitive differentiation in 3D. Ultimately, as volume adaptation is ubiquitous in 3D microenvironments in vivo, new tools will lead the way in analyzing and understanding mechanobiology.

Abstract: Melanoma is the fourth most commonly diagnosed cancer in Australia, resulting in ~1500 deaths each year. While extensive public health campaigns have increased community awareness of the importance of sun-safety and skin monitoring, a substantial number of melanomas remain undetected until late-stage progression. New treatments that harness the immune system offer great promise for melanoma treatment, but further advances are required for these approaches to succeed in the majority of patients. Immunotherapy strategies use a variety of approaches to harness T cell immunity to control melanoma. We have recently identified several new settings of effective T cell cancer surveillance, resulting in either complete elimination of malignant cells or the establishment of a dynamic ‘melanoma-immune equilibrium’. This fundamental knowledge should be of value for the development of novel clinical strategies targeting cancer.

Speaker: Dr. Jason Waithman is a molecular and cellular immunologist having obtained his PhD in 2008. His training was completed in outstanding institutions that include the University of Melbourne, Walter and Eliza Hall Institute, and Ludwig Institute for Cancer Research under the guidance of multiple international leading immunologists. He relocated to Perth in 2012 to establish and run an independent, original research program at the Telethon Kids Institute. He has successfully attracted fellowship support from 2010-21 and has attracted project funding from multiple sources to support his research program. He is currently working closely with an industry partner and the host institute to develop innovative therapeutic techniques for cancer patients as part of the discovery and translation pipeline associated with his research program.