Dr Evelyne Deplazes is a Chancellor’s Research Fellow at the School of Life Sciences at the University of Technology Sydney (UTS) and an Adjunct Research Fellow at the School of Pharmacy and Biomedical Sciences at Curtin University (Perth). She received her PhD in computational biophysics from the University of Western Australia in 2012. Subsequently, she was awarded an Early Career Fellowship (ECF) by the Swiss National Science Foundation, followed by an Early Career Fellowship form the Australian National Health and Research Council (NHMRC) to work at the University of Queensland. During her postdoctoral research she developed her interest in venom peptides and peptide-based drug design. In 2016, Dr Deplazes moved to Curtin University to pursue her independent research projects, which she now continues at UTS.
Apart from her research Dr Deplazes is passionate about supporting diversity and equity in science as well as teaching the next generation of scientists to be 'critical thinkers'.
Dr Deplazes' research sits at the interface of chemistry, biophysics, pharmaceutical and computational science.Through her work she has developed strong analytical and problem solving skills and is experienced in translating knowledge gained from fundamental science into rational drug design approaches. Her excellent communication skills and mindful approach to leadership enable her engage with scientists and stakeholders from different fields to address complex challenges. Dr Deplazes has also worked with media teams from the WA Cancer council to attract more than $80k in donations for cancer research.
Dr Deplazes is actively involved in her scientific community and has been on several conference organising committees. From 2016-2018 she was a member of the WA committee of the Australian Society for Medical research. Dr Deplazes is a current member and website administrator of the Australian Society for Biophysics as well as the secretary of the Australasian Molecular Modelling society.
Can supervise: YES
Dr Deplazes’ sits at the interface of (bio)chemistry, structural biology, biophysics and computer science and spans from the 'basic' science of understanding fundamental processes to working with researchers in molecular biology and pharmacology. Her research combines computer simulations and biophysics experiments to understand how peptides derived from animals and plants interact with cell membranes and how we can use this to develop new pharmaceutical approaches to treating cancer, infectious diseases and neurological disorders. At the heart of her research lies her curiosity to understand the molecular world and the vision for her work to contribute to a healthier Australia.
Keywords: venom peptides, drug design, computational biophysics, biomolecular simulations, membranes.
May main teaching activities include the principles of protein structure and biomolecular interactions as well as introduction to techniques used to study proteins and other biomolecules (both 'wet-lab' and 'in silico').
Deplazes, E, White, J, Murphy, C, Cranfield, CG & Garcia, A 2019, 'Competing for the same space: protons and alkali ions at the interface of phospholipid bilayers.', Biophysical reviews, vol. 11, no. 3, pp. 483-490.View/Download from: UTS OPUS or Publisher's site
Maintaining gradients of solvated protons and alkali metal ions such as Na+ and K+ across membranes is critical for cellular function. Over the last few decades, both the interactions of protons and alkali metal ions with phospholipid membranes have been studied extensively and the reported interactions of these ions with phospholipid headgroups are very similar, yet few studies have investigated the potential interdependence between proton and alkali metal ion binding at the water-lipid interface. In this short review, we discuss the similarities between the proton-membrane and alkali ion-membrane interactions. Such interactions include cation attraction to the phosphate and carbonyl oxygens of the phospholipid headgroups that form strong lipid-ion and lipid-ion-water complexes. We also propose potential mechanisms that may modulate the affinities of these cationic species to the water-phospholipid interfacial oxygen moieties. This review aims to highlight the potential interdependence between protons and alkali metal ions at the membrane surface and encourage a more nuanced understanding of the complex nature of these biologically relevant processes.
Deplazes, E, Chin, YK-Y, King, GF & Mancera, RL 2019, 'The unusual conformation of cross-strand disulfide bonds is critical to the stability of beta-hairpin peptides', PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS.View/Download from: Publisher's site
Deplazes, E, Poger, D, Cornell, B & Cranfield, CG 2018, 'The effect of H3O+ on the membrane morphology and hydrogen bonding of a phospholipid bilayer', Biophysical Reviews, vol. 10, no. 5, pp. 1371-1376.View/Download from: Publisher's site
© 2018, International Union for Pure and Applied Biophysics (IUPAB) and Springer-Verlag GmbH Germany, part of Springer Nature. At the 2017 meeting of the Australian Society for Biophysics, we presented the combined results from two recent studies showing how hydronium ions (H3O+) modulate the structure and ion permeability of phospholipid bilayers. In the first study, the impact of H3O+ on lipid packing had been identified using tethered bilayer lipid membranes in conjunction with electrical impedance spectroscopy and neutron reflectometry. The increased presence of H3O+ (i.e. lower pH) led to a significant reduction in membrane conductivity and increased membrane thickness. A first-order explanation for the effect was assigned to alterations in the steric packing of the membrane lipids. Changes in packing were described by a critical packing parameter (CPP) related to the interfacial area and volume and shape of the membrane lipids. We proposed that increasing the concentraton of H3O+ resulted in stronger hydrogen bonding between the phosphate oxygens at the water–lipid interface leading to a reduced area per lipid and slightly increased membrane thickness. At the meeting, a molecular model for these pH effects based on the result of our second study was presented. Multiple μs-long, unrestrained molecular dynamic (MD) simulations of a phosphatidylcholine lipid bilayer were carried out and showed a concentration dependent reduction in the area per lipid and an increase in bilayer thickness, in agreement with experimental data. Further, H3O+ preferentially accumulated at the water–lipid interface, suggesting the localised pH at the membrane surface is much lower than the bulk bathing solution. Another significant finding was that the hydrogen bonds formed by H3O+ ions with lipid headgroup oxygens are, on average, shorter in length and longer-lived than the ones formed in bulk water. In addition, the H3O+ ions resided for longer periods in association with the carb...
Deplazes, E, Poger, D, Cornell, B & Cranfield, CG 2018, 'The effect of hydronium ions on the structure of phospholipid membranes.', Physical Chemistry Chemical Physics, vol. 20, no. 1, pp. 357-366.View/Download from: UTS OPUS or Publisher's site
This work seeks to identify the mechanisms by which hydronium ions (H3O+) modulate the structure of phospholipid bilayers by studying the interactions of H3O+ with phospholipids at the molecular level. For this, we carried out multiple microsecond-long unrestrained molecular dynamics (MD) simulations of a POPC bilayer at different H3O+ concentrations. The results show that H3O+ accumulates at the membrane surface where it displaces water and forms strong and long-lived hydrogen bonds with the phosphate and carbonyl oxygens in phospholipids. This results in a concentration-dependent reduction of the area per lipid and an increase in bilayer thickness. This study provides an important molecular-level insight into the mechanism of how H3O+ modulates the structure of biological membranes and is a critical step towards a better understanding of the effect of low pH on mammalian and bacterial membranes.
© 2018 Wiley Periodicals, Inc. Because of their wide range of biological activities venom peptides are a valuable source of lead molecules for the development of pharmaceuticals, pharmacological tools and insecticides. Many venom peptides work by modulating the activity of ion channels and receptors or by irreversibly damaging cell membranes. In many cases, the mechanism of action is intrinsically linked to the ability of the peptide to bind to or partition into membranes. Thus, understanding the biological activity of these venom peptides requires characterizing their membrane binding properties. This review presents an overview of the recent developments and challenges in using biomolecular simulations to study venom peptide-membrane interactions. The review is focused on (i) gating modifier peptides that target voltage-gated ion channels, (ii) venom peptides that inhibit mechanosensitive ion channels, and (iii) pore-forming venom peptides. The methods and approaches used to study venom peptide-membrane interactions are discussed with a particular focus on the challenges specific to these systems and the type of questions that can (and cannot) be addressed using state-of-the-art simulation techniques. The review concludes with an outlook on future aims and directions in the field.
Fernandez-Rojo, MA, Deplazes, E, Pineda, SS, Brust, A, Marth, T, Wilhelm, P, Martel, N, Ramm, GA, Mancera, RL, Alewood, PF, Woods, GM, Belov, K, Miles, JJ, King, GF & Ikonomopoulou, MP 2018, 'Gomesin peptides prevent proliferation and lead to the cell death of devil facial tumour disease cells.', Cell death discovery, vol. 4.View/Download from: UTS OPUS or Publisher's site
The Tasmanian devil faces extinction due to devil facial tumour disease (DFTD), a highly transmittable clonal form of cancer without available treatment. In this study, we report the cell-autonomous antiproliferative and cytotoxic activities exhibited by the spider peptide gomesin (AgGom) and gomesin-like homologue (HiGom) in DFTD cells. Mechanistically, both peptides caused a significant reduction at G0/G1 phase, in correlation with an augmented expression of the cell cycle inhibitory proteins p53, p27, p21, necrosis, exacerbated generation of reactive oxygen species and diminished mitochondrial membrane potential, all hallmarks of cellular stress. The screening of a novel panel of AgGom-analogues revealed that, unlike changes in the hydrophobicity and electrostatic surface, the cytotoxic potential of the gomesin analogues in DFTD cells lies on specific arginine substitutions in the eight and nine positions and alanine replacement in three, five and 12 positions. In conclusion, the evidence supports gomesin as a potential antiproliferative compound against DFTD disease.
Moore, SJ, Sonar, K, Bharadwaj, P, Deplazes, E & Mancera, RL 2018, 'Characterisation of the Structure and Oligomerisation of Islet Amyloid Polypeptides (IAPP): A Review of Molecular Dynamics Simulation Studies.', Molecules (Basel, Switzerland), vol. 23, no. 9.View/Download from: UTS OPUS or Publisher's site
Human islet amyloid polypeptide (hIAPP) is a naturally occurring, intrinsically disordered protein whose abnormal aggregation into amyloid fibrils is a pathological feature in type 2 diabetes, and its cross-aggregation with amyloid beta has been linked to an increased risk of Alzheimer's disease. The soluble, oligomeric forms of hIAPP are the most toxic to β-cells in the pancreas. However, the structure of these oligomeric forms is difficult to characterise because of their intrinsic disorder and their tendency to rapidly aggregate into insoluble fibrils. Experimental studies of hIAPP have generally used non-physiological conditions to prevent aggregation, and they have been unable to describe its soluble monomeric and oligomeric structure at physiological conditions. Molecular dynamics (MD) simulations offer an alternative for the detailed characterisation of the monomeric structure of hIAPP and its aggregation in aqueous solution. This paper reviews the knowledge that has been gained by the use of MD simulations, and its relationship to experimental data for both hIAPP and rat IAPP. In particular, the influence of the choice of force field and water models, the choice of initial structure, and the configurational sampling method used, are discussed in detail. Characterisation of the solution structure of hIAPP and its mechanism of oligomerisation is important to understanding its cellular toxicity and its role in disease states, and may ultimately offer new opportunities for therapeutic interventions.
Schumann-Gillett, A, Mark, AE, Deplazes, E & O'Mara, ML 2018, 'A potential new, stable state of the E-cadherin strand-swapped dimer in solution.', European biophysics journal : EBJ, vol. 47, no. 1, pp. 59-67.View/Download from: UTS OPUS or Publisher's site
E-cadherin is a transmembrane glycoprotein that facilitates inter-cellular adhesion in the epithelium. The ectodomain of the native structure is comprised of five repeated immunoglobulin-like domains. All E-cadherin crystal structures show the protein in one of three alternative conformations: a monomer, a strand-swapped trans homodimer and the so-called X-dimer, which is proposed to be a kinetic intermediate to forming the strand-swapped trans homodimer. However, previous studies have indicated that even once the trans strand-swapped dimer is formed, the complex is highly dynamic and the E-cadherin monomers may reorient relative to each other. Here, molecular dynamics simulations have been used to investigate the stability and conformational flexibility of the human E-cadherin trans strand-swapped dimer. In four independent, 100 ns simulations, the dimer moved away from the starting structure and converged to a previously unreported structure, which we call the Y-dimer. The Y-dimer was present for over 90% of the combined simulation time, suggesting that it represents a stable conformation of the E-cadherin dimer in solution. The Y-dimer conformation is stabilised by interactions present in both the trans strand-swapped dimer and X-dimer crystal structures, as well as additional interactions not found in any E-cadherin dimer crystal structures. The Y-dimer represents a previously unreported, stable conformation of the human E-cadherin trans strand-swapped dimer and suggests that the available crystal structures do not fully capture the conformations that the human E-cadherin trans homodimer adopts in solution.
Tanner, JD, Deplazes, E & Mancera, RL 2018, 'The Biological and Biophysical Properties of the Spider Peptide Gomesin.', Molecules (Basel, Switzerland), vol. 23, no. 7.View/Download from: UTS OPUS or Publisher's site
This review summarises the current knowledge of Gomesin (Gm), an 18-residue long, cationic anti-microbial peptide originally isolated from the haemocytes of the Brazilian tarantula Acanthoscurria gomesiana. The peptide shows potent cytotoxic activity against clinically relevant microbes including Gram-positive and Gram-negative bacteria, fungi, and parasites. In addition, Gm shows in-vitro and in-vivo anti-cancer activities against several human and murine cancers. The peptide exerts its cytotoxic activity by permeabilising cell membranes, but the underlying molecular mechanism of action is still unclear. Due to its potential as a therapeutic agent, the structure and membrane-binding properties, as well as the leakage and cytotoxic activities of Gm have been studied using a range of techniques. This review provides a summary of these studies, with a particular focus on biophysical characterisation studies of peptide variants that have attempted to establish a structure-activity relationship. Future studies are still needed to rationalise the binding affinity and cell-type-specific selectivity of Gm and its variants, while more pre-clinical studies are required to develop Gm into a therapeutically useful peptide.
Agwa, AJ, Lawrence, N, Deplazes, E, Cheneval, O, Chen, RM, Craik, DJ, Schroeder, CI & Henriques, ST 2017, 'Spider peptide toxin HwTx-IV engineered to bind to lipid membranes has an increased inhibitory potency at human voltage-gated sodium channel hNa(v)1.7', BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, vol. 1859, no. 5, pp. 835-844.View/Download from: Publisher's site
Agwa, AJ, Lawrence, N, Deplazes, E, Cheneval, O, Chen, RM, Craik, DJ, Schroeder, CI & Henriques, ST 2017, 'Spider peptide toxin HwTx-IV engineered to bind to lipid membranes has an increased inhibitory potency at human voltage-gated sodium channel hNa(V)1.7 (vol 1859, pg 835, 2017)', BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, vol. 1859, no. 11, pp. 2277-2277.View/Download from: Publisher's site
Deplazes, E, Davies, J, Bonvin, AMJJ, King, GF & Mark, AE 2016, 'Combination of Ambiguous and Unambiguous Data in the Restraint driven Docking of Flexible Peptides with HADDOCK: The Binding of the Spider Toxin PcTx1 to the Acid Sensing Ion Channel (ASIC) 1a', JOURNAL OF CHEMICAL INFORMATION AND MODELING, vol. 56, no. 1, pp. 127-138.View/Download from: Publisher's site
Deplazes, E, Henriques, ST, Smith, JJ, King, GF, Craik, DJ, Mark, AE & Schroeder, CI 2016, 'Membrane-binding properties of gating modifier and pore-blocking toxins: Membrane interaction is not a prerequisite for modification of channel gating', BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, vol. 1858, no. 4, pp. 872-882.View/Download from: Publisher's site
Henriques, ST, Deplazes, E, Lawrence, N, Cheneval, O, Chaousis, S, Inserra, M, Thongyoo, P, King, GF, Mark, AE, Vetter, I, Craik, DJ & Schroeder, CI 2016, 'Interaction of Tarantula Venom Peptide ProTx-II with Lipid Membranes Is a Prerequisite for Its Inhibition of Human Voltage-gated Sodium Channel Na(V)1.7', JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 291, no. 33, pp. 17049-17065.View/Download from: Publisher's site
Deplazes, E, Begg, SL, van Wonderen, JH, Campbell, R, Kobe, B, Paton, JC, MacMillan, F, McDevitt, CA & O'Mara, ML 2015, 'Characterizing the conformational dynamics of metal-free PsaA using molecular dynamics simulations and electron paramagnetic resonance spectroscopy', BIOPHYSICAL CHEMISTRY, vol. 207, pp. 51-60.View/Download from: Publisher's site
Saez, NJ, Deplazes, E, Cristofori-Armstrong, B, Chassagnon, IR, Lin, X, Mobli, M, Mark, AE, Rash, LD & King, GF 2015, 'Molecular dynamics and functional studies define a hot spot of crystal contacts essential for PcTx1 inhibition of acid-sensing ion channel 1a', BRITISH JOURNAL OF PHARMACOLOGY, vol. 172, no. 20, pp. 4985-4995.View/Download from: Publisher's site
Ujvari, B, Casewell, NR, Sunagar, K, Arbuckle, K, Wuester, W, Lo, N, O'Meally, D, Beckmann, C, King, GF, Deplazes, E & Madsen, T 2015, 'Widespread convergence in toxin resistance by predictable molecular evolution', PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, vol. 112, no. 38, pp. 11911-11916.View/Download from: Publisher's site
Walczewska-Szewc, K, Depazes, E & Corry, B 2015, 'Comparing the Ability of Enhanced Sampling Molecular Dynamics Methods To Reproduce the Behavior of Fluorescent Labels on Proteins', JOURNAL OF CHEMICAL THEORY AND COMPUTATION, vol. 11, no. 7, pp. 3455-3465.View/Download from: Publisher's site
Martinac, B, Nomura, T, Chi, G, Petrov, E, Rohde, PR, Battle, AR, Foo, A, Constantine, M, Rothnagel, R, Carne, S, Deplazes, E, Cornell, B, Cranfield, CG, Hankamer, B & Landsberg, MJ 2014, 'Bacterial mechanosensitive channels: models for studying mechanosensory transduction.', Antioxidants and Redox Signaling, vol. 20, no. 6, pp. 952-969.View/Download from: UTS OPUS or Publisher's site
SIGNIFICANCE: Sensations of touch and hearing are manifestations of mechanical contact and air pressure acting on touch receptors and hair cells of the inner ear, respectively. In bacteria, osmotic pressure exerts a significant mechanical force on their cellular membrane. Bacteria have evolved mechanosensitive (MS) channels to cope with excessive turgor pressure resulting from a hypo-osmotic shock. MS channel opening allows the expulsion of osmolytes and water, thereby restoring normal cellular turgor and preventing cell lysis. RECENT ADVANCES: As biological force-sensing systems, MS channels have been identified as the best examples of membrane proteins coupling molecular dynamics to cellular mechanics. The bacterial MS channel of large conductance (MscL) and MS channel of small conductance (MscS) have been subjected to extensive biophysical, biochemical, genetic, and structural analyses. These studies have established MscL and MscS as model systems for mechanosensory transduction. CRITICAL ISSUES: In recent years, MS ion channels in mammalian cells have moved into focus of mechanotransduction research, accompanied by an increased awareness of the role they may play in the pathophysiology of diseases, including cardiac hypertrophy, muscular dystrophy, or Xerocytosis. FUTURE DIRECTIONS: A recent exciting development includes the molecular identification of Piezo proteins, which function as nonselective cation channels in mechanosensory transduction associated with senses of touch and pain. Since research on Piezo channels is very young, applying lessons learned from studies of bacterial MS channels to establishing the mechanism by which the Piezo channels are mechanically activated remains one of the future challenges toward a better understanding of the role that MS channels play in mechanobiology.
Nomura, T, Cranfield, CG, Deplazes, E, Owen, DM, Macmillan, A, Battle, AR, Constantine, M, Sokabe, M & Martinac, B 2012, 'Differential effects of lipids and lyso-lipids on the mechanosensitivity of MscL and MscS', Proceedings of The National Academy of Sciences of the United States of America, vol. 109, no. 22, pp. 8770-8775.View/Download from: UTS OPUS or Publisher's site
Mechanosensitive (MS) channels of small (MscS) and large (MscL) conductance are the major players in the protection of bacterial cells against hypoosmotic shock. Although a great deal is known about structure and function of these channels, much less is known about how membrane lipids may influence their mechanosensitivity and function. In this study,we use liposome coreconstitution to examine the effects of different types of lipids on MscS and MscL mechanosensitivity simultaneously using the patch-clamp technique and confocal microscopy. Fluorescence lifetime imaging (FLIM)-FRET microscopy demonstrated that coreconstitution of MscS and MscL led to clustering of these channels causing a significant increase in the MscS activation threshold. Furthermore, the MscL/MscS threshold ratio dramatically decreased in thinner compared with thicker bilayers and upon addition of cholesterol, known to affect the bilayer thickness, stiffness and pressure profile. In contrast, application of micromolar concentrations of lysophosphatidylcholine (LPC) led to an increase of the MscL/MscS threshold ratio. These data suggest that differences in hydrophobic mismatch and bilayer stiffness, change in transbilayer pressure profile, and close proximity of MscL and MscS affect the structural dynamics of both channels to a different extent. Our findings may have far-reaching implications for other types of ion channels and membrane proteins that, like MscL and MscS, may coexist in multiple molecular complexes and, consequently, have their activation characteristics significantly affected by changes in the lipid environment and their proximity to each other.
Deplazes, E, Louhivuori, M, Jayatilaka, D, Marrink, SJ & Corry, B 2012, 'Structural Investigation of MscL Gating Using Experimental Data and Coarse Grained MD Simulations', PLOS COMPUTATIONAL BIOLOGY, vol. 8, no. 9.View/Download from: Publisher's site
Deplazes, E, Jayatilaka, D & Corry, B 2011, 'Testing the use of molecular dynamics to simulate fluorophore motions and FRET', PHYSICAL CHEMISTRY CHEMICAL PHYSICS, vol. 13, no. 23, pp. 11045-11054.View/Download from: Publisher's site
Deplazes, E, van Bronswijk, W, Zhu, F, Barron, LD, Ma, S, Nafie, LA & Jalkanen, KJ 2008, 'A combined theoretical and experimental study of the structure and vibrational absorption, vibrational circular dichroism, Raman and Raman optical activity spectra of the L-histidine zwitterion', THEORETICAL CHEMISTRY ACCOUNTS, vol. 119, no. 1-3, pp. 155-176.View/Download from: Publisher's site