Contact
Biography
Joern Steinert studied at the Humboldt University Berlin and graduated in 1996 with the Diplom in Biophysics. Following his PhD in Vascular Biology at King's College London (1997-2001), he took up postdoctoral positions in Tuebingen (2002) and Heidelberg (2004) to study physiological mechanisms of neurotransmission using mammalian and Drosophila model systems. After a position as a Senior Investigator with Prof Ian Forsythe at the MRC Toxicology Unit Leicester, he became Program Leader at the same Institute before starting an Assistant Professor position at the University of Nottingham in 2020. His research focuses on the regulation of neuronal excitability under activity-dependent mechanisms involving nitric oxide signaling and how regulation of the redox homeostasis in neurodegeneration associated with neuroinflammation impacts on neuropathology such as in Alzheimer's disease.
Dr Steinert is an Associate Editor for Cell Death Discovery and acts as a Review and Associate Editor for Frontiers in Molecular Neuroscience and Frontiers in Synaptic Neuroscience, in addition to serving as a Guest Editor for several journals including Free Radical Biology and Medicine, The Journal of Physiology and Cell Death Disease. He is an Associate Fellow of Higher Education UK (AFHEA), Fellow Member of the Physiological Society, UK and member of the BNA, UK, Society for Redox Biology and Medicine (SfRBM) and European Drosophila Society (EDRC). He organized/chaired Symposia at the Annual Physiological Society UK Main Meeting, the Main Conference of the SFRR-Europe and FENS meeting.
ResearchGate
Expertise Summary
Our lab predominantly applies neurophysiological methodologies to study neuronal and synaptic plasticity and function as well as ion channel regulation. My main expertise lies in the electrophysiological assessment of neuronal function coupled with live imaging including measurements of intracellular calcium and nitric oxide and ATP dynamics.
We use mammalian model systems of disease, generate brain slice preparations for studying neuronal function and correlate data with behavioral phenotypes; Drosophila models are also used for optogenetic, electrophysiological and morphological studies to address specific research questions related to synaptic signaling. Several behavioral studies in adult flies and larvae include learning&memory and activity (circadian, negative geotaxis, locomotor) testing.
Models used in the lab: Drosophila melanogaster and mouse to study neuronal and synaptic function in health and disease including nitric oxide and related redox signaling.
Schematic of Nitric Oxide signaling at the synapse:
Morphology of the Drosophila neuromuscular junction (NMJ, blue-DAPI, red-BRP, green-HRP):
Comparison of the effects of NO on glutamatergic synaptic transmission in mouse and fly:
Activity of LNv neurons in the Drosophila CNS:
Current lab members:
Aelfwin Stone (PhD)
Jennifer Cale (PhD)
Vlada Yarosh (MRes)
Megan de Lange (MRes)
Maria Haig (technical support)
Teaching Summary
Module Convenor For Neurobiology of Disease (LIFE/2071):
Dopamine pathways
Drugs of abuse, addiction and reward
Autism spectrum disorder
Neurobiology of circadian and sleep disorders
Co-existent neurotransmission salivary secretion
ADHD, stimulant and non- stimulant medication
Schizophrenia
Parkinson's disease and its treatment
Serotonergic pathways
Neuropeptides
HPA-axis endocrine regulation
Migraine and emesis
Neuroinflammation
Gut Brain Axis
Neurobiology and treatment of Schizophrenia
Neurobiology and treatment of sleep and endocrine dysfunction
Research Summary
I am interested in investigating pathways involved in regulating neuronal and synaptic function and dysfunctional signalling in neurodegeneration associated with neuroinflammation. I investigate… read more
Selected Publications
BOURGOGNON, JULIE-MYRTILLE, SPIERS, JEREME G, ROBINSON, SUE W, SCHEIBLICH, HANNAH, GLYNN, PAUL, ORTORI, CATHARINE, BRADLEY, SOPHIE J, TOBIN, ANDREW B and STEINERT, JOERN R, 2021. Inhibition of neuroinflammatory nitric oxide signaling suppresses glycation and prevents neuronal dysfunction in mouse prion disease. Proceedings of the National Academy of Sciences of the United States of America. 118(10), SPIERS, JEREME G., BREDA, CARLO, ROBINSON, SUE, GIORGINI, FLAVIANO and STEINERT, JOERN R., 2019. Drosophila Nrf2/Keap1 Mediated Redox Signaling Supports Synaptic Function and Longevity and Impacts on Circadian Activity FRONTIERS IN MOLECULAR NEUROSCIENCE. 12, SPIERS, JEREME G., CHEN, HSIAO-JOU CORTINA, BOURGOGNON, JULIE-MYRTILLE and STEINERT, JOERN R., 2019. Dysregulation of stress systems and nitric oxide signaling underlies neuronal dysfunction in Alzheimer's disease FREE RADICAL BIOLOGY AND MEDICINE. 134, 478-493 BOURGOGNON, JULIE-MYRTILLE, SPIERS, JEREME G., SCHEIBLICH, HANNAH, ANTONOV, ALEXEY, BRADLEY, SOPHIE J., TOBIN, ANDREW B. and STEINERT, JOERN R., 2018. Alterations in neuronal metabolism contribute to the pathogenesis of prion disease CELL DEATH AND DIFFERENTIATION. 25(8), 1408-1425
We are currently inviting applications for self-funded MRes and BBSRC DTP-funded (BBSRC DTP UoN) PhD projects (UoN guidelines and requirements):
1. The contribution of a high fat diet to sporadic Alzheimer's Disease mediated via the gut-brain axis communication in Drosophila.
Key aims:
- to identify the mechanisms by which a high fat diet (HFD) causes a cholesterol- and ApoE4-mediated Aß42 production via altering APP and secretase interactions.
- to test if a HFD exacerbates AD pathology in genetically predisposed animals.
- to test if administration of probiotics ameliorates the dietary-induced pathology thereby alleviating AD hallmarks.
2. Investigating the neurobiological mechanisms of psychedelics and their potential to treat affective disorders in Drosophila and mouse model.
Key aims:
1. Generation and characterisation of fly strains to test the effects of disrupted monoaminergic neuronal activity: A range of Drosophila lines will be established which exhibit altered monoaminergic and glutamatergic transmission. We will identify the effects of receptor and precursor knock-outs/knock-downs/overexpression (i.e. serotonin receptor, tryptophan hydroxylase and amino acid decarboxylase) in subsets of neurons to establish phenotypes assess at neuronal and behavioural levels. Electrophysiological and live imaging (calcium imaging: GCaMP6s, FRET imaging: cAMP) studies will investigate neuronal activity and be complement by behavioural studies.
2. Elucidation the target pathways of psychedelic actions: Measurements (physiology, imaging) of neuronal activities and whole animal behaviours will be assessed using the above lines in the presence of various psychedelics. This will define the circuits and subpopulations of neurons which are involved in responses to psychedelic actions.
3. Translational validation in mouse studies: The above information will allow us to interrogate specific neuronal networks and transmitter pathways in mouse which are affected by psychedelic actions. We will apply specific pharmacology to identify serotonergic signalling causing behavioural phenotypes of psychedelics and complement these findings with in vitro brain slice electrophysiology to characterise corresponding changes in neuronal activity.
Current Research
I am interested in investigating pathways involved in regulating neuronal and synaptic function and dysfunctional signalling in neurodegeneration associated with neuroinflammation. I investigate molecular mechanisms of neuronal dysfunction in mice developing neurodegeneration which display classical phenotypes of protein-misfolding pathologies such as occurring in Alzheimer's, Parkinson's and Creutzfeldt-Jakob disease (prion-misfolding). I also utilise advantages of the Drosophila model organism to study synaptic effects of protein misfolding and redox signalling, as well as optogenetic approaches to manipulate neuronal activities, thus using complementary models to study neuronal function. In order to gain deeper insides into underlying and early-onset dysfunctional pathways in neurodegeneration, I have assessed the metabolome in hippocampal and cortical tissues from prion-diseased mice. These data showed vast amounts of alterations in the neuronal metabolism, including glycolysis, arginine and prostaglandin pathways and oxidative stress signalling amongst many others. Importantly, dysfunction of these pathways has also been highlighted as predisposing and causal conditions during aging, thereby further facilitating and increasing the risk of developing neurodegenerative pathologies. I have a strong interest in elucidating the mechanisms by which redox stress modulates neuronal function developed new exciting projects related to neuroinflammation, redox and cellular stress signalling which includes oxidative and nitrergic stress.