The balanced brain: two-photon microscopy of inhibitory synapse formation
Coordination between excitatory and inhibitory synapses (providing positive and negative signals respectively) is required to ensure proper information processing in the brain. Many brain disorders, especially neurodevelopental disorders, are rooted in a specific disturbance of this coordination. In my research group we use a combination of two-photon microscopy and electrophisiology to examine how inhibitory synapses are fromed and how this formation is coordinated with nearby excitatroy synapses.
Improving the assessment of SYNGAP1 and related genetic conditions by creating online measures for parents and patients
Developing metal-based radiopharmaceuticals for imaging and therapy
Personalised medicine will be greatly enhanced with the introduction of new radiopharmaceuticals for the diagnosis and treatment of various cancers, as well as cardiovascular disease and brain disorders. The unprecedented interest in developing theranostic radiopharmaceuticals is mainly due to the recent clinical successes of radiometal-based products including: • 177LuDOTA-TATE (trade name Lutathera, FDA approved in 2018), a peptide-based tracer that is used for treating metastatic neuroendocrine tumours • Ga 68 PSMA-11 (FDA approved in 2020), a positron emission tomography agent for imaging prostate-specific membrane antigen positive lesions in men with prostate cancer. In this webinar, Dr Brett Paterson and PhD candidate Mr Cormac Kelderman will present their research on developing the chemistry and radiochemistry to produce new radiometal-based imaging and therapy agents. They will discuss the synthesis of new molecules, the optimisation of the radiochemistry, and results from preclinical evaluations. Dr Brett Paterson is a National Imaging Facility Fellow at Monash Biomedical Imaging and academic group leader in the School of Chemistry, Monash University. His research focuses on the development of radiochemistry and new radiopharmaceuticals. Cormac Kelderman is a PhD candidate under the supervision of Dr Brett Paterson in the School of Chemistry, Monash University. His research focuses on developing new bis(thiosemicarbazone) chelators for technetium-99m SPECT imaging.
Neuro-Immune Coupling: How the Immune System Sculpts Brain Circuitry
In this lecture, Dr Stevens will discuss recent work that implicates brain immune cells, called microglia, in sculpting of synaptic connections during development and their relevance to autism, schizophrenia and other brain disorders. Her recent work revealed a key role for microglia and a group of immune related molecules called complement in normal developmental synaptic pruning, a normal process required to establish precise brain wiring. Emerging evidence suggests aberrant regulation of this pruning pathway may contribute to synaptic and cognitive dysfunction in a host of brain disorders, including schizophrenia. Recent research has revealed that a person’s risk of schizophrenia is increased if they inherit specific variants in complement C4, gene plays a well-known role in the immune system but also helps sculpt developing synapses in the mouse visual system (Sekar et al., 2016). Together these findings may help explain known features of schizophrenia, including reduced numbers of synapses in key cortical regions and an adolescent age of onset that corresponds with developmentally timed waves of synaptic pruning in these regions. Stevens will discuss this and ongoing work to understand the mechanisms by which complement and microglia prune specific synapses in the brain. A deeper understanding of how these immune mechanisms mediate synaptic pruning may provide novel insight into how to protect synapses in autism and other brain disorders, including Alzheimer’s and Huntington’s Disease.
SynGAP modulates the body's biological clock: What Syngap1 mice can tell us about light & sleep
Innate immune response in brain pathologies: Lost in translation?
Inflammation is a key component of the innate immune response. Primarily designed to remove noxious agents and limit their detrimental effects, the prolonged and/or inappropriately scaled innate immune response may be detrimental to the host and lead to a chronic disease. Indeed, there is increasing evidence suggesting that a chronic deregulation of immunity may represent one of the key elements in the pathobiology of many brain disorders. Microglia are the principal immune cells of the brain. The consensus today is that once activated microglia/macrophages can acquire a wide repertoire of profiles ranging from the classical pro-inflammatory to alternative and protective phenotypes. Recently, we described a novel ribosome-based regulatory mechanism/checkpoint that controls innate immune gene translation and microglial activation involving RNA binding protein SRSF3. Here we will discuss the implications of SRSF3 and other endogenous immune regulators in deregulation of immunity observed in different models of brain pathologies. Furthermore, we will discuss whether targeting SRSF3 and mRNA translation may open novel avenues for therapeutic modulation of immune response in the brain.
From genetics to neurobiology through transcriptomic data analysis
Over the past years, genetic studies have uncovered hundreds of genetic variants to be associated with complex brain disorders. While this really represents a big step forward in understanding the genetic etiology of brain disorders, the functional interpretation of these variants remains challenging. We aim to help with the functional characterization of variants through transcriptomic data analysis. For instance, we rely on brain transcriptome atlases, such as Allen Brain Atlases, to infer functional relations between genes. One example of this is the identification of signaling mechanisms of steroid receptors. Further, by integrating brain transcriptome atlases with neuropathology and neuroimaging data, we identify key genes and pathways associated with brain disorders (e.g. Parkinson's disease). With technological advances, we can now profile gene expression in single-cells at large scale. These developments have presented significant computational developments. Our lab focuses on developing scalable methods to identify cells in single-cell data through interactive visualization, scalable clustering, classification, and interpretable trajectory modelling. We also work on methods to integrate single-cell data across studies and technologies.
European University for Brain and Technology Virtual Opening
The European University for Brain and Technology, NeurotechEU, is opening its doors on the 16th of December. From health & healthcare to learning & education, Neuroscience has a key role in addressing some of the most pressing challenges that we face in Europe today. Whether the challenge is the translation of fundamental research to advance the state of the art in prevention, diagnosis or treatment of brain disorders or explaining the complex interactions between the brain, individuals and their environments to design novel practices in cities, schools, hospitals, or companies, brain research is already providing solutions for society at large. There has never been a branch of study that is as inter- and multi-disciplinary as Neuroscience. From the humanities, social sciences and law to natural sciences, engineering and mathematics all traditional disciplines in modern universities have an interest in brain and behaviour as a subject matter. Neuroscience has a great promise to become an applied science, to provide brain-centred or brain-inspired solutions that could benefit the society and kindle a new economy in Europe. The European University of Brain and Technology (NeurotechEU) aims to be the backbone of this new vision by bringing together eight leading universities, 250+ partner research institutions, companies, societal stakeholders, cities, and non-governmental organizations to shape education and training for all segments of society and in all regions of Europe. We will educate students across all levels (bachelor’s, master’s, doctoral as well as life-long learners) and train the next generation multidisciplinary scientists, scholars and graduates, provide them direct access to cutting-edge infrastructure for fundamental, translational and applied research to help Europe address this unmet challenge.
Common developmental mechanisms underlie multiple brain disorders linked to corpus callosum dysgenesis. (Simultaneous translation to Spanish)
The corpus callosum is the largest fibre tract in the brain of placental mammals and connects the two cerebral hemispheres. Corpus callosum dysgenesis is a developmental brain disorder that is commonly genetic and occurs in approximately 1:4000 live births. It is easily diagnosed by MRI or prenatal ultrasound and is found in isolation or together with other brain anomalies, or with other organ system defects in a large number of different congenital syndromes. Callosal dysgenesis is a structural brain wiring disorder that can impact brain function and cognition in heterogeneous ways. We aim to understand how early developmental mechanisms lead to circuit alterations that ultimately impact behaviour and cognition. Translated to Spanish by MD and Medical interpreter Trinidad Ott. El cuerpo calloso es el tracto de fibras más grande del cerebro de los mamíferos placentarios y conecta los dos hemisferios cerebrales. La disgenesia del cuerpo calloso es un trastorno del desarrollo del cerebro que comunmente es genético y ocurre en aproximadamente 1: 4000 nacidos vivos. Se diagnostica fácilmente mediante resonancia magnética o ecografía prenatal y se encuentra aislado o junto con otras anomalías cerebrales, o con otros defectos del sistema de órganos en un gran número de síndromes congénitos diferentes. La disgenesia callosa es un trastorno estructural del cableado cerebral que puede afectar la función cerebral y la cognición de formas heterogéneas. Nuestro objetivo es comprender cómo los primeros mecanismos del desarrollo conducen a alteraciones en los circuitos que, en última instancia, afectan el comportamiento y la cognición. Traducción al español por la Doctora e Intérprete Médica Trinidad Ott.