ADB2021

With ~700 million individuals affected by chronic kidney disease (CKD) globally and no antifibrotic treatment currently approved for CKD patients, there is an urgent need to develop better models of human fibrotic kidneys to accelerate the discovery of novel therapies. In this regard, organoids have a proven ability to replicate aspects of genetic ...

Background: Androgen deprivation therapy is the primary treatment for advanced prostate cancer. Despite sustained suppression of androgens, patients eventually develop castration-resistant prostate cancer and require further treatment. A new treatment is Bipolar Androgen Therapy (BAT), where patients rapidly cycle between castrate and supraphysiolo...

Introduction: There is growing attention on uncertainty tolerance (UT) as a medical training competency, including assessment with UT scales. Yet little is known about how medical students experience uncertainty, nor factors that impact UT development. Accordingly, this research asked: ‘How do medical students experience and manage (i.e. tolerate) ...

The aim of my PhD project is to examine the masticatory system of Neanderthals from a functional and biomechanical point of view. By carrying out 3D modelling of bones and teeth from a wide Neanderthal and modern human fossil sample and by virtually reconstruct the simulation of their chewing behaviour, I will be able to assess if Neanderthal crani...

Realizing the full potential of single cell RNA sequencing (scRNA-seq) in biomedical science has been hindered by the high cost of experiments, a lack of spatial context, and limited capacity to analyze the resulting data. This project will focus on developing robust methods and analysis pipelines to address these challenges in the context of ki...

The Caenorhabditis elegans (C. elegans) germline is an efficient reproduction system driven by a GLP-1/Notch regulatory network to control germ cell proliferation and differentiation. It shares multiple features with germlines of other animals, such as the existence of a self-renewing germline stem cell population. By examining the C. elegans germl...

Pattern recognition receptors (PRRs) play a vital role in the detection of pathogens and danger signals within the innate immune system. Cyclic GMP-AMP synthase (cGAS) acts as PRR that detects cytosolic dsDNA, a common hallmark of infection. Additionally, cGAS can also recognise host dsDNA that leaks from the mitochondria or nuclei. Detection of ds...

Mesenchymal stromal cells, also referred to as (mesenchymal stem cells; MSCs), are ideal candidates for regenerative medicine and cellular therapeutics due to several qualities they possess. Nowadays, MSCs are the subject of extensive research to explore their best applicable potential, and pinpoint the keys these cells hold that can open doors in ...

Over recent years, the Hippo signalling pathway has emerged as a regulator of key developmental processes, including organ size and tissue growth. Initially identified in the fruit fly, Drosophila melanogaster, this evolutionarily conserved signalling pathway comprises of over 35 components, each fitting into a complex network feeding a central kin...

Induced pluripotent stem cells (iPSCs), which are derived through the process of reprogramming from human somatic cells, have the potential to differentiate into any cell type of the body. iPSCs can be cultured in a naive state that resembles the preimplantation epiblast, or a primed state that resembles the post-implantation epiblast. In a recent ...

Multiple sclerosis is a non-traumatic debilitating disease of the central nervous system (CNS) that affects approximately 2,500,000 people globally and is currently incurable. It is characterised by repeated autoimmune attacks directed at oligodendrocytes and the myelin they produce. This demyelinating disease is characterised by immune dysregulati...

Estrogen receptor positive (ER+) breast cancer (BCa) is the most commonly occurring BCa subtype (>70%). Though survival rates are >95% due to improvements in treatment strategies, the incidence of disease continues to rise despite current risk reducing/preventative strategies in place. One prevention strategy offered to women at high risk of ER+ BC...

Conventional cytotoxic cancer therapies exert permanent damage to the ovary; hence, loss of fertility is a major concern for female reproductive-age cancer survivors. However, the landscape of cancer therapies is rapidly changing, with attention shifting to more personalised, targeted treatments. Immunotherapies, like checkpoint inhibitors anti-PD-...

Mitochondrial stress responses are essential molecular mechanisms that maintain homeostasis when an organism is faced with stress. Local stress responses can be communicated to distal tissues to enable global reactions to challenges, thereby increasing the chance of organismal survival. The nervous system is critical for coordinating systemic stres...

Endosomal trafficking in single cells is built of generation of membrane vesicles, their motor protein mediated transport, morphological alterations such as tubulation, fusion and fission, and dynamic maintenance of various identities, which is defined by the lipid composition and localization of specific proteins on them. Endosomal maturation is a...

Normal functioning of the gastrointestinal tract involves the communication between multiple essential cell types located in close proximity, such as epithelial cells and the enteric nervous system (ENS). Studies have shown that intestinal epithelial stem cells express neurotransmitter receptors that may directly modulate stem cell fate and epithel...

Stimulator of Interferon Genes (STING) is a critical component of the innate immune response against microbial infection. Activation of STING is induced following the recognition of pathogen-associated molecular patterns (PAMPs) present within the host cell cytosol during infection. Following activation, STING signalling promotes the expression of ...

The Endosomal-network begins at the plasma membrane following endocytosis by undergoing successive fusion resulting in maturation. The Rab effector proteins APPL1 and EEA1 drive endosomes towards the peri-nuclear cloud. The first part of the Ph.D. thesis establishes the role of APPL1 and dynein specific to endosome maturation. The second part addre...

Lattice light-sheet microscopy, a rapid volumetric imaging technique, acquires images using a plane of excitation which results in images being acquired at an oblique angle. For a typical acquisition of two colour movies of endosomal trafficking at 4 volumes per second for 20 min, about 20 TB of data is generated. Visualisation of the data to adjud...

Cellular identity is ultimately dictated by the interaction of transcription factors with regulatory elements (REs) to control gene expression. Genome-wide epigenome profiling techniques have significantly increased our understanding of cell-specific utilization of REs. However, it remains difficult to dissect the majority of factors interacting wi...

Anatomical pathology is a critical specialty in the tissue diagnosis of diseases, such as cancers. A current and anticipated anatomical pathology workforce shortage is predicted to delay diagnoses and the commencement of urgent treatment required for patients. A cause of this workforce shortage has been a deficiency in professional identity develop...

In the past decade, mesenchymal stromal cells (MSCs) have developed a substantial portfolio in clinical trials, becoming the focus of many regenerative immunotherapies. Besides being multipotent and having self-renewal capacity, MSCs possess anti-inflammatory properties. However, the mechanisms underlying their immunosuppressive effects remain poor...

Liquid liquid phase separation (LLPS) is a biological phenomenon whereby proteins separate out from the liquid cytoplasm into a phase separated compartment or “droplet”. These droplets are highly concentrated in protein and represent a dynamic environment in which proteins can easily flow in and out of. However, what causes a protein to phase separ...

Molecular dissection of epigenetic and epitranscriptomic pathways in gene regulation for the maintenance of the embryonic stem cells state Varun Pandey, Pratibha Tripathi, Partha Pratim Das Epigenetics and Gene Regulation Laboratory,Monash Biomedicine Discovery Institute, Department of Anatomy and Developmental Biology, Monash University, Cla...

Mesenchymal stromal cells (MSCs) have anti-inflammatory and tissue-reparative potentials. As such, MSCs present as a therapeutic cell type in inflammatory diseases. However, the mechanisms underlying their immunoregulatory effects are not well understood. MSC secretomes are thought to mediate their therapeutic effects. Recent studies from our lab a...

miR-9/29a/107 are key players in neurodegeneration. Hence, we foresee that identifying the upstream regulators of our miRNA biogenesis through QTL mapping in cc mice will reveal the genetic architecture behind this phenomenon. Further, functional studies from Neural Progenitor cells isolated from the hippocampus will identify roles in neurogenesis....

The ability of cells to sense energy status and coordinate mitochondrial metabolism for energy homeostasis is critical for organismal development and survival. Mitochondrial calcium signaling has emerged as a key mediator of mitochondrial bioenergetics. Currently there is a significant knowledge gap regarding how mitochondrial calcium is adjusted t...

Almost all multicellular organisms have two sexes that exhbit dimorphic molecular and morphological characteristics. Development, including sexually dimorphic development is regulated by transcription factors. In the nematode Caenorhabditis elegans, sexually dimorphic characteristics are regulated by transcription factors from Doublesex DNA Domain ...

Aging, as a time-dependent physiological functional decline, is driven by multiple factors, and is accompanied by an increased risk of many chronic diseases, such as cardiovascular disorders, diabetes, cancer, and some neurodegeneration diseases. Among all age-related functional decline, locomotion impairment is one of the most prominent outcomes. ...

NSUN2 mediates m5C RNA methylation to control gene regulatory functions for maintaining the self-renewal of murine embryonic stem cells state Michael Bullen, Yogesh Kumar, Pratibha Tripathi and Partha Das Epitranscriptomic or RNA epigenetic modifications take place at the post-transcriptional level in transcribed RNAs without altering any R...

Purpose: Several lines of evidence from non-vertebrate organisms suggest TOP3A is critical for quality control in oocytes, with roles in the repair of meiotic DNA double strand breaks and DNA damage, and in the maintenance of mitochondrial DNA (mtDNA). Whilst compelling, the role of TOP3A in the gametes of mammalian species has never been establi...

In vivo time-lapse microscopy allows us to capture vast amounts of data that, with the aid of computational methods can allow us to delineate the mechanisms underpinning biological processes. In order to extract high quality quantitative data from these sorts of images, we need to develop accurate methods to finding and tracking objects of interest...

Defective placental development is the primary cause of the great obstetric syndromes (GOSs) and is a major contributor to intrauterine lethality. However, the mechanisms of human placental development are largely unknown. Recently developed protocols have allowed the maintenance of human placental trophoblast stem cells (TSCs) in vitro that demons...

Human pluripotent and trophoblast stem cells have been essential alternatives to blastocysts for understanding early human development. However, these simple culture systems lack the complexity to adequately model the spatiotemporal cellular and molecular dynamics that occur during early embryonic development. Here we describe the reprogramming of ...