Keynote Speakers
Prof. Richard Simerly
Prof. Richard Simerly (Vanderbilt University, US) - 16 February 2023 09:10 - 09:45 (CET)
Developmental Neurobiology of Neural Circuits Controlling Feeding Behavior
Hunger is a basic survival state that shapes much of the activities in the living world. As in other goal directed behaviors, food intake involves decisions resulting from neural integration of signals from the external environment (e.g. sight, taste, smell) and interosensory information that signals internal state to the brain. Interosensory information is conveyed to key circuit nodes responsible for goal directed behaviors by a complex system of neural connections, and the activity of these pathways has a significant impact on prioritization of external cues and adaptive responses. Hypothalamic neural networks maintain energy homeostasis by coordinating endocrine signals with behavioral and autonomic functions to ensure that behaviors and physiological responses remain in tune with environmental demands. Because the architecture of neural circuits determines how they function, a comprehensive understanding of how neural systems responsible for neuroendocrine integration are organized is essential, and we are working to determine how developmental events impact their construction and functional properties. By evaluating the impact of early hormonal and nutritional challenges on the brain wide organization of these essential neural systems, and by profiling neuronal responses to varied interosensory stimuli in vivo, we are gaining insight into neurobiological mechanisms underlying developmental programming of neuroendocrine integration, within the functional context of feeding behavior.
Prof. Sharona E. Gordon
Prof. Sharona E. Gordon (University of Washington School of Medicine, US) - 16 February 2023 16:45 – 17:20 (CET)
Real-time traffic: new optical tools for measuring exocytosis and endocytosis applied to TRPV1 ion channels
The sensitivity of peripheral pain-receptor neurons to noxious thermal and chemical stimuli is tuned by a variety of receptors and second messengers, in part through tuning the sensitivity and number of TRPV1 ion channels that act as receptors for thermal and chemical stimuli. The gain can be decreased, producing desensitization, or increased, producing hyperalgesia. Over the last decade, significant progress has been made in understanding both desensitization and hyperalgesia at the cellular and molecular levels. This talk will focus on the mechanisms regulating plasma membrane density of TRPV1 ion channels. Nerve growth factor released onto sensory neurons during inflammation triggers a signaling cascade that increases the number of TRPV1 ion channels in the neuronal plasma membrane. The increased number of channels make the cell more sensitive to noxious TRPV1 activators. We have recently developed new click chemistry tools to label TRPV1 channels on the cell surface with unprecedented speed and specificity. Together with genetic code expansion to incorporate noncanonical amino acid click substrates into TRVP1 and optogenetic methods to manipulate the nerve growth factor signaling cascade, these tools allow us to dissect the steps of TRPV1 trafficking– or any membrane protein – in living cells in real time.
Prof. Lea Sistonen
Prof. Lea Sistonen (Åbo Akademi University. Turku Centre for Biotechnology, FI) - 17 February 2023 09:05 – 09:40 (CET)
Stress-type specific genome-wide transcription programs of genes and enhancers
Cellular stress triggers re-programming of transcription, which is fundamental for the maintenance of protein homeostasis, also called proteostasis, under adverse growth conditions. Stress-induced changes in transcription include induction of cytoprotective genes and repression of genes related to the regulation of the cell cycle, transcription programs, and metabolism. Induction of transcription is mediated through the activation of stress-responsive transcriptions factors that facilitate the release of stalled RNA polymerase II, thereby allowing for transcriptional elongation. Repression of transcription, in turn, involves components that retain RNA polymerase II in a paused state in gene promoters. Moreover, transcription during stress is regulated by a massive activation of enhancers and complex changes in chromatin organization. Heat shock has provided an excellent model to investigate the mechanisms of nascent transcription, but less is known about the transcriptional regulation upon other types of cellular stress. Therefore, we examined re-programming of genes and enhancers in response to two distinct stresses, i.e. oxidative stress and heat shock by combining different genome-wide analyses (PRO-seq and ChIP-seq). This approach allowed determining the target repertoire of specific members of the heat shock factor (HSF) family. We found that HSF1 and HSF2 drive stress-type specific transcription programs and that besides functioning as promoter-binding transcription factors, both HSFs activate genes through enhancers in response to oxidative stress and heat shock. Intriguingly, in contrast to the promoter-bound HSF1, which regulates classical chaperone genes, recruitment of HSF1 to enhancers is required for the induction of genes encoding proteins that reside in the plasma membrane. It is also plausible that the capacity of HSFs to orchestrate transcription via enhancers is not limited to stress responses, since HSFs play important roles also in developmental and pathological processes, such as progression of cancer.
Prof. Giles Yeo
Prof. Giles Yeo (University of Cambridge, UK) - 15 February 2023 - 13:10 – 13:45 (CET)
Is obesity a choice?
It is clear that the cause of obesity is a result of eating more than you burn. It is physics. What is more complex to answer is why some people eat more than others? Differences in our genetic make-up mean some of us are slightly more hungry all the time and so eat more than others. In contrast to the prevailing view, obesity is not a choice. People who are obese are not bad or lazy; rather, they are fighting their biology.
