Dr Fekade Sime and Dr Stephanie Miller

Dr Fekade Sime

Title: In vitro infection models for the development and optimisation of antibiotic regimens

Bio: Dr. Sime acquired his PhD degree in Pharmacy in 2015 from the University of South Australia. In Jan 2016, he was awarded a Post-Doctoral Fellowship at the University of Queensland and recently a NHMRC Emerging Leadership-1 Investigator Grant (2021-2025). He is currently working as a Research Fellow and Laboratory Manager at the Centre for Translational Anti-infective Pharmacodynamics, School of Pharmacy, the University of Queensland. His research involves the application of advanced in vitro infection model pharmacodynamics, clinical pharmacokinetics, and mathematical modelling for optimisation of antimicrobial therapy in special patient populations.

Overview: The development of antibiotics and optimisation of their clinical utility requires a multi-stage research spanning from in vitro infection models to large scale randomised controlled trials. This talk will discuss the critical role of advanced in vitro infections models at all stages of antibiotic development including the post-marketing optimisation of dosing regimens for treatment of multi-drug resistant infections. It will outline available local research capabilities and the potential for collaboration.

Dr Stephanie Miller

Title: Potassium Chloride Co-transporter after Neonatal Hypoxia and Hypothermia

Bio: Dr Miller is an early career researcher who was awarded her PhD in Neuroscience in January 2018 from The University of Queensland. She has continued her research in the field of Neuroscience with Dr Tracey Bjorkman in the Newborn Brain Injury and Repair lab group at UQ Centre for Clinical Research. Her research interests include HI-injury and neonatal seizures, and preterm brain injury. Investigating alterations to receptors and transporters, and neuroinflammatory mechanisms after neonatal HI or preterm birth will help elucidate therapeutic strategies to alleviate newborn brain injuries.

Overview: Hypoxic ischaemic encephalopathy (HIE) is the most common cause of mortality and morbidity in the newborn. In the hypoxic-ischaemic (HI) brain, over-activation of excitatory neurotransmitter systems plays a key role in the generation of seizures and excitotoxic neuronal cell injury and cell death.  There are few options to alleviate HI brain injury in term infants, and clinically is limited to the application of therapeutic hypothermia, and symptomatically treating other post-HI events such as seizures. During brain development there is an imbalance towards excitatory neurotransmission, with the activation of GABA_A receptors resulting in excitation in immature neurons, rather than inhibition. The polarity of the GABA_A receptor results from the intracellular chloride concentration, created with the import or extrusion of chloride across the cell membrane. The Potassium-Chloride co-transporter (KCC2) extrudes chloride ions from the neuron, and immature neurons have high intracellular chloride, due to lower KCC2 expression.  Whereas mature neurons have lower intracellular chloride concentrations, driven by the developmental upregulation of KCC2 expression. Events in the neonatal period – such as HIE, may disrupt the developmentally regulated expression of KCC2.  We investigated the effect of perinatal hypoxia on KCC2 expression in our preclinical piglet model and examined the effect of therapeutic hypothermia after HI.