Philip Poronnik

The University of Sydney

Designing technologies in the palliative care environment is difficult due to the sensitivity of the context and vulnerability of the patients and their families in a critical stage of life. We conducted two focus groups with 9 healthcare workers to capture sociotech-nical imaginaries to support physical, psychological, social and spiritual aspects...

Biomedical science students need to learn to code. Graduates face a future where they will be better prepared for research higher degrees and the workforce if they can code. Embedding coding in a biomedical curriculum comes with challenges. First, biomedical science students often experience anxiety learning quantitative and computational thinking...

A fifth of healthcare professionals experience violence perpetrated against them every year by patients or their family members [1]. In response to the violence and aggression challenges faced in the Western Sydney Local Health District (WSLHD), we conducted a study to identify clinician experiences to guide the restructuring of the Code Black resp...

BACKGROUND Violence and aggression are significant challenges faced by clinicians globally. Traditional methods of training consist of “on the job learning” and role play simulations. While both approaches can result in improved skill levels they are not without limitation. Interactive simulations using VR can complement traditional training proces...

Background: Violence and aggression are significant workplace challenges faced by clinicians worldwide. Traditional methods of training consist of “on-the-job learning” and role-play simulations. Although both approaches can result in improved skill levels, they are not without limitation. Interactive simulations using virtual reality (VR) can comp...

This brief review provides insights into the recent advances made by the Unity game engine into education and the ways that learning resources can be used to teach novice bioscience students to use the VR/AR affordances of the platform. We present our own practises for implementation of a novel gamification task for final-year bioscience students a...

--------------------------------------------------------------------------------------------------------------------------------------- https://www.frontiersin.org/articles/10.3389/fdgth.2021.628452/full --------------------------------------------------------------------------------------------------------------------------------------- The COVI...

This brief review explores the ever-increasing role that technological affordances may play in the 21C biochemistry and molecular biology curriculum. We consider the need to develop digital and creative fluencies in our students and the importance of creativity and visualization in learning science. The potential of virtual reality (VR) platforms t...

Background: As technological innovation increases the availability of novel therapeutic options in general practice, healthcare professionals will need to equip themselves with a sound understanding of their professional legal duties in light of emerging medical technologies, including virtual reality (VR). Objective: Using a case study of VR to...

Background: Traditional methods of delivering Advanced Life Support (ALS) training and reaccreditation are resource-intensive and costly. Interactive simulations and gameplay using virtual reality (VR) technology can complement traditional training processes as a cost-effective, engaging, and flexible training tool. Objective: This exploratory s...

BACKGROUND Traditional methods of delivering Advanced Life Support (ALS) training and reaccreditation are resource-intensive and costly. Interactive simulations and gameplay using virtual reality (VR) technology can complement traditional training processes as a cost-effective, engaging, and flexible training tool. OBJECTIVE This exploratory study...

The delivery of ongoing training and support to Advanced Life Support (ALS) teams poses significant resourcing and logistical challenges. A reduced exposure to cardiac arrests and mandated re-accreditation pose further challenges for educators to overcome. This work presents the ALS-SimVR (Advanced Life Support Simulation in VR) application. The ap...

Virtual Reality (VR) is now consumer ready and nearing ubiquity. In terms of clinical applications, several studies suggest that VR can be effective as a complementary adjunct or alternative non-pharmacologic analgesic in a range of pain-inducing procedures and in management of chronic pain. The increasing affordability and quality of portable VR h...

The ubiquitin proteasome system (UPS) plays an important role in regulating numerous cellular processes, and a dysfunctional UPS is thought to contribute to motor neuron disease. Consequently, we sought to map the changing ubiquitome in human iPSCs during their pluripotent stage and following differentiation to motor neurons. Ubiquitinomics analysi...

Students commencing tertiary studies in life sciences over the next decade are going to arrive at universities with a more advanced digital literacy and shifting expectations of how technology supports learning. This poses a challenge to traditional approaches to tertiary science education. As the increasingly digitally literate students arrive, an...

As Australian universities welcome significant numbers of inbound international students and increasingly encourage outbound domestic student mobility, the opportunities for global discipline connectedness, cross-cultural understandings, and fertile learning interactions abound. Yet these two “strands” of students rarely engage in deliberately orga...

Aim: Albumin can be covalently modified at surface lysine residues and thus the circulation contains a mixture of native albumin (i.e. not modified) and albumin with varying degrees of modification. Uptake and lysosomal degradation of glomerular filtered albumin by proximal tubular cells via the megalin scavenger receptor is considered an importan...

Tubular epithelial cells take up and degrade plasma albumin filtered by the glomerulus. Tubular damage resulting in reduced albumin uptake or degradation has been suggested as one mechanism contributing to albuminuria in kidney disease. This study investigated whether albumin uptake or degradation is altered in acute and chronic glomerular disease....

[This corrects the article DOI: 10.1371/journal.pone.0174431.].

Proteins identified in the rat liver ubiquitome for each condition. (XLSX)

Ubiquitin is a crucial post-translational modification regulating numerous cellular processes, but its role in metabolic disease is not well characterized. In this study, we identified the in vivo ubiquitin-modified proteome in rat liver and determined changes in this ubiquitome under acute insulin stimulation and high-fat and sucrose diet-induced...

Protein-protein interactome of the total liver ubiquitome. (TIF)

Insulin stimulation alters the hfsd ubiquitome of the rat liver. (A) Venn diagram of proteins ubiquitinated in High-Fat Sucrose Diet (HFSD) compared to HFSD + Insulin. (B) Ontology analysis of identified ubiquitinylated proteins. (C) STRING analysis of differentially ubiquitinated proteins. (TIF)

Proteins identified in the rat liver ubiquitome for each condition. (XLSX)

Statistical workflow. Flow diagram showing data analysis method from mass spectrometry raw data. (TIF)

Proteomics data variability analysis. (A) Histograms showing peptide abundance distributions in individual replicates for each condition. (B) Multiple regression analysis of peptide abundance in individual replicates. (TIF)

Effects of diet on insulin stimulated ubiquitome of the rat liver. (A) Venn diagram of proteins ubiquitinated in Chow + Insulin compared to High-Fat Sucrose Diet (HFSD) + Insulin. (B) Ontology analysis of identified ubiquitinylated proteins. (C) STRING analysis of differentially ubiquitinated proteins. (TIF)

Venn analysis of proteins identified in each replicate. (TIF)

Ubiquitinated proteins unique to each condition. (XLSX)

Proteins ubiquitinated in response to insulin. (XLSX)

Three alternative sonifications of proteomic data distributions were compared as a means to indicate the neuropathology associated with Amyotrophic Lateral Sclerosis (ALS) via auditory display (through exploration of the differentiation of induced pluripotent stem cell derived neurons). Pure visual displays of proteomic data often result in ”visual...

We tackle the important problem of understanding the accuracy of activity tracker data. To do this, we introduce the notions of daily and hourly adherence, key aspects of how consistently people wear trackers. We hypothesise that these measures provide a valuable means to address accuracy problems in population level activity tracking data. To test...

Danger exists in using deficit and decline narratives that unsurprisingly have paralleled evidenced declines in research funding for Australian science. While surveys suggest a public lack of understanding of science which is all too often diagnosed and remediated as “dumbness”, Australians value science education. Scientists need to be careful whe...

The structural organisation of pancreatic beta cells in the islets of Langerhans is relatively unknown. Here, using 3D two-photon, 3D confocal and 3D block-face serial electron microscopy, we demonstrate a consistent in situ polarisation of beta cells and define three distinct cell-surface domains. An apical domain located at the vascular apogee of...

The consolidation of short-term memory into long-term memory involves changing protein level and activity for the synaptic plasticity required for long-term potentiation (LTP). AMPA receptor trafficking is a key determinant of LTP and recently ubiquitination by Nedd4 has been shown to play an important role via direct action on the GluA1 subunit, a...

The constitutive uptake and degradation of filtered albumin by the proximal tubule has resulted in this process being relegated a passive player in albuminuria. Real-time intravital imaging of the rat kidney now describes a new paradigm in which the proximal tubule dynamically increases or decreases albumin uptake following changes in plasma albumi...

The consumption of a high fat diet (HFD) is associated with proteinuria and altered sodium handling and excretion, which can lead to kidney disease. In the proximal tubule, the Na(+) /H(+) Exchanger 3 (NHE3) is responsible for normal protein reabsorption and the reabsorption of approximately 70% of the renal sodium load. It is the Na(+) /K(+) -ATPa...

ClC-5 is a chloride/proton exchanger that plays an obligate role in albumin uptake by the renal proximal tubule. ClC-5 forms an endocytic complex with the albumin receptor megalin/cubilin. We have identified a novel ClC-5 binding partner, aspartyl-aminopeptidase (DNPEP), that catalyses the release of N-terminal aspartate/glutamate residues. The phy...

Learning spaces can play a powerful role in shaping and supporting the activities of the students and teachers who use them: they can be agents for change when the success of new pedagogical approaches depends on shifting entrenched practices. The laboratory is a key site for science education. It is here that discipline knowledge and generic compe...

It is well known that TGF-β1 plays a central role in renal fibrosis due in large part to stimulation of inflammatory responses. KCa3.1, a potassium channel protein, has been suggested as a potential therapeutic target for diseases such as sickle cell anemia, autoimmunity, atherosclerosis and more recently, kidney fibrosis. Blockade of KCa3.1 has be...

Nedd4 is a widely expressed ubiquitin ligase that is necessary for normal neuronal development and function. However, largely due to the lethality of Nedd4 homozygous knockout mice, little is known about the physiological roles of Nedd4 in the adult brain. In this study we used Nedd4 heterozygous mice, which are viable and live to maturity, to asse...

Background: The cannabinoid receptor type 2 (CB2) is reduced in podocytes of animals and humans with Type 2 Diabetes Mellitus (T2DM), with activation of CB2 ameliorating albuminuria in animals. As albuminuria also is due to proximal tubule dysfunction, the aim of this study is to investigate tubular expression of CB2 under diabetic conditions in ad...

Nedd4-2, a HECT-type ubiquitin-protein ligase, has been implicated in regulating several ion channels, including voltage-gated sodium (Nav) channels. In Xenopus oocytes Nedd4-2 strongly inhibits the activity of multiple Navs. However, the conditions under which Nedd4-2 mediates native Nav regulation remain uncharacterised. Using Nedd4-2 deficient m...

Adipocytes secrete a number of bioactive adipokines that activate a variety of cell signaling pathways in central and peripheral tissues. Obesity is associated with altered production of many adipokines which is linked to a number of pathologies. As an increase in body weight is directly associated with an increased risk for developing chronic kidn...

Leptin plays a pathophysiological role in the kidney, however, its acute effects on the proximal tubule cells (PTCs) are unknown. In opossum kidney (OK) cells in vitro, Western blot analysis identified that exposure to leptin increases the phosphorylation of the mitogen-activated protein kinase (MAPK) p44/42and the mammalian target of rapamysin (mT...

Background and purpose: Albuminuria is an important biomarker of renal dysfunction and is a major mediator of renal damage and fibrosis during kidney disease. The mechanisms underlying albumin-induced renal fibrosis remain unclear. There has been significant interest in γ-secretase activity in tubular epithelial cells in recent times; however, its...

Neurotensin receptors (NT-R) and the epidermal growth factor receptors (EGF-R) are commonly overexpressed in many epithelial origin tumours. In addition to their role as mitogenic mediators through specific cell signalling, recent studies indicate that the activity/expression of scaffold proteins responsible for the assembly and coordination of the...

Background/aims: Receptor-mediated endocytosis of albumin by the renal proximal tubule requires a number of proteins including megalin/cubilin, sodium/hydrogen exchanger isoform 3 (NHE3) and ClC-5, as well as the PSD-95/Dlg/Zo-1 (PDZ) scaffold sodium/hydrogen exchanger regulatory factor 2 (NHERF2). Despite members from the AGC kinase family, v-Akt...

The current paradigm of G protein coupled receptor signaling involves a classical pathway being the activation of phospholipase C and the generation of 1,4,5-inositol trisphosphate, signaling through β-arrestin scaffold molecules and the transactivation of tyrosine kinase growth factor receptors. Transactivation greatly expands the range of signali...

The choroid plexus is a structure within each ventricle of the brain that is composed of fenestrated vessels surrounded by secretory epithelial cells. The epithelial cells are linked by tight junctions to create a permeability barrier. The epithelial cells are derived from neuroectoderm, and are thus defined by some authors as a subtype of macrogli...

GLAST (EAAT1) is an abundant glial glutamate transporter in the mammalian brain. It plays important roles in terminating excitatory transmission in grey matter, as well as pathophysiological roles, including protecting white matter from excitotoxic injury. In normal brain, alternative splicing of GLAST has been described: GLAST1a and GLAST1b arise...

The scavenger receptor megalin binds to albumin in the microvilli of the renal proximal tubule, and transports the ligand to the intravillar cleft for processing by endocytosis. Albumin endocytosis in the proximal tubule is regulated by protein complexes containing a number of transmembrane and accessory proteins including PDZ scaffolds such as NHE...

Despite the abundant expression of protease-activated receptor-2 (PAR-2) by the kidney, its relevance to renal physiology and pathophysiology is unclear. Recent studies have demonstrated a role for this receptor in infl ammation and cell proliferation in nonrenal tissues. The aims of this study were to establish if human proximal tubule cells, (PTC...

The electrical excitability of neurons is mediated primarily by voltage-gated ion channels, particularly voltage-gated Na(+) (Na(v)), K(+) (K(v)) and Cl(-) (ClC) channels. Cells regulate their electrical excitability by controlling not only the activity, but also the number of individual ion channels in the plasma membrane. There exist several mech...

Since its first characterization in the erythrocyte membrane the plasma membrane Ca(2+)-ATPase has been well-defined as a ubiquitous mechanism for the efflux of Ca(2+) from eukaryotic cells. With 4 isoforms and potentially 30 splice variants, defining the absolute physiological role of plasma membrane Ca(2+)-ATPase has been difficult and very limit...

We have examined brains of neonatal pigs that were rendered hypoxic. Glutamine synthetase (GS), a key enzyme in the detoxification of glutamate and ammonia, was rapidly lost from astrocytes in regions susceptible to damage, including the CA1 of hippocampus and various cortical regions. Conversely, resilient areas such as the dentate gyrus exhibited...

We have previously reported that P2Y(2) purinoceptors and muscarinic M(3) receptors trigger Ca(2+) responses in HT-29 cells that differ in their timecourse, the Ca(2+) response to P2Y(2) receptor activation being marked by a more rapid decline of intracellular Ca(2+) concentration ([Ca(2+)](i)) after the peak response and that this rapid decline of...

Efflux of cytosolic Ca2+ mediated by plasma membrane Ca2+-ATPases (PMCA) plays a key role in fine tuning the magnitude and duration of Ca2+ signaling following activation of G-protein-coupled receptors. However, the molecular mechanisms that underpin the trafficking of PMCA to the membrane during Ca2+ signaling remain largely unexplored in native c...

Albuminuria is a key marker of renal injury and a major risk factor for cardiovascular disease. In vivo imaging techniques with fluorescent albumin have allowed visualization of its movement within the whole kidney but they could not distinguish between intact and degraded albumin. To visualize albumin degradation in proximal tubular cells in vivo...

The voltage-gated KCNQ2/3 and KCNQ3/5 K(+) channels regulate neuronal excitability. We recently showed that KCNQ2/3 and KCNQ3/5 channels are regulated by the ubiquitin ligase Nedd4-2. Serum- and glucocorticoid-regulated kinase-1 (SGK-1) plays an important role in regulation of epithelial ion transport. SGK-1 phosphorylation of Nedd4-2 decreases the...

The Tweety proteins comprise a family of chloride ion channels with three members identified in humans (TTYH1-3) and orthologues in fly and murine species. In humans, increased TTYH2 expression is associated with cancer progression, whereas fly Tweety is associated with developmental processes. Structurally, Tweety proteins are characterized by fiv...

The role of angiotensin II (Ang II) in mediating excessive sodium reabsorption in diabetic nephropathy is recognized. Serine-glucocorticoid kinase-1 (SGK-1) increases sodium-hydrogen exchanger-3 (NHE3) expression and is known to be upregulated in in vitro and in vivo models of diabetic nephropathy. However, a link between Ang II and SGK-1 in diabet...

This article takes as its starting point the ongoing downturn in student interest in, and engagement with, the enabling sciences. We make a case that embedding of creative pedagogies in science education has significant potential to arrest the flight from modern science. Five propositions are explored in order to argue the case: that young people a...

Transforming growth factor-beta(1) (TGFbeta(1)) is recognized as both a fibrogenic and inflammatory cytokine and plays a critical role in the kidney pathophysiology. The dysregulation of TGFbeta(1) has been linked with the development of diabetic nephropathy. Connective tissue growth factor (CTGF) is a fibrogenic cytokine and is recognized as a dow...