EMBL Seminars

Abstract
Transporting small molecules across cell membranes is an essential process in cell physiology. The uptake of glucose and the maintenance of intracellular pH are two fundamental processes carried out by most cells. Here, I will present our multidisciplinary approach that has revealed important insights into the mechanism of glucose (GLUT) uptake and Na+/H+ exchange, which are important transport systems for our cells to utilize glucose as an energy source and for the regulation cytoplasmic and organellar pH. I will also present our recent structural insights into a sperm-specific Na+/H+ exchanger regulated by voltage – transforming the transporter into a signaling cascade that is essential in animals (metazoa) for sperm motility and fertilization. Nature (2023). 623:193–201; Nature. (2020) 578 (7794):321-325; Nature (2015) 526(7573):397-401; Nature (2013) 501(7468):573-7.

About the speaker
Prof. David Drew hails from New Zealand where he obtained a MSc in Chemistry from Auckland University. He joined the lab of Prof. de Gier at Stockholm University for his PhD thesis research where he developed a technique of using GFP to monitor membrane protein topology and over expression in E. coli. After a EMBO post-doc fellowship at Imperial College London, he started his own research group as a University Royal Society (URF) Fellow at Imperial, focusing on structural studies of glucose (GLUT) transporters. In 2013, Drew returned to Stockholm University where he currently resides as a Wallenberg Scholar. Drew is internationally recognized by his pioneering structural studies of glucose transporters and Na+/H+ exchangers, membrane protein GFP-based methods, and influential reviews on small molecule transport. Drew has been acknowledged with several prizes, including the Göran Gustafsson Prize in Chemistry from the Swedish Royal Academy of Science, the Arrhenius medal from the Swedish Chemistry Society and EMBO membership.

Connection details
Zoom*: https://embl-org.zoom.us/j/96262723506?pwd=L1BNci9CcFNkREU5ZEpqUXZ1YTR1dz09

(Meeting ID: [962 6272 3506], Password: [753770])

Please note that the talk will not be recorded.
*For the FAQ section, as a zoom participant, please use either the chat function (the host will read out your question) or the “raise your hand” function and turn on your microphone.

Abstract
The molecular mechanisms causing neuronal death in many neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) and Charcot Marie Tooth (CMT) disease, are poorly understood. The key consequence of our incomplete understanding of disease pathogenesis is that there is a complete dearth of effective symptomatic treatments for these widespread global disorders, prompting the necessity for a step-change in treatment strategies to fight these pathologies.

In this view, we are investigating ALS and CMT as disease paradigms to identify new, common targets for pharmacological intervention in these devastating pathologies. Recently, we uncovered alterations in axonal transport of several cytoplasmic organelles, such as mitochondria and signalling endosomes, at pre-symptomatic stages of ALS and CMT pathogenesis, suggesting that these impairments may play a causative role in disease onset and progression. Crucially, we have restored axonal transport to physiological levels at early symptomatic stages of disease, thus demonstrating that these pathological changes are fully reversible. 

In light of these promising results, our main goal is identifying novel signalling nodes that modulate axonal transport in healthy and diseased neurons. This will allow us to test the hypothesis that counteracting axonal transport deficits observed in ALS, CMT and other neurodegenerative diseases, represents a novel, effective therapeutic strategy towards treating these pathologies.

Abstract
Optimal performance, in which a task is completed quickly and accurately, is difficult to achieve and maintain.  Is this because the neural pathways underlying the performance need to be accurately tuned through plasticity, or is it because of variability in the state of the brain?  Here we present evidence that waking mice are constantly in a state of flux – ranging from a state of low arousal and inattentiveness, to high arousal and stress.  The optimal state for performance of sensory detection or discrimination tasks lies in the middle – optimally aroused, attentive, and appropriately activated, but to some degree relaxed.  Rapid variations in the waking state of the animal, which occur on time scales as short as 10s of milliseconds, involve an interaction of the thalamus and cerebral cortex, controlled by neurotransmitter pathways that remain to be clearly delineated  These rapid changes in state can account for a significant portion of on-going activity in the mammalian brain, and therefore need to be fully understood and accounted for.

Abstract
 

Chromosome segregation is performed by the spindle, a dynamic machine composed of microtubules, motors, and other associated proteins (MAPs). We currently know a lot about the protein components what constitute the spindle. However, evolution has tuned these components differently in different organisms. I will present different strategies that yeast, insect, and human cells have evolved to assemble the spindle for chromosome segregation. Understanding these different modes of spindle assembly may help fight cancer.

About the speaker
[Biographical information about the speaker].

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Attachments
[Link to a file (for example a pdf of the seminar’s programme) - the file can be uploaded on the intranet]

Connection details
Zoom*: [link] (Meeting ID: [XXXXXXXXX], Password: [XXXXXXX])

Please note that the talk will yes/not be recorded.
*For the FAQ section, as a zoom participant, please use either the chat function (the host will read out your question) or the “raise your hand” function and turn on your microphone.

Abstract
The centriole is an evolutionary conserved organelle coordinating fundamental biological processes including cell division, cellular signaling and cell motility. This organelle, of 500 nm long and 250 nm in diameter is composed of about 200 different proteins, some of which have been associated with human diseases. How these proteins are organized at the level of the centriole architecture and how associated mutations could be involved in pathologies is still poorly understood. In this seminar, I will present the latest work from my laboratory, which tackle these fundamental structural cell biology questions using cryo-tomography, cell biology and our newly developed ultrastructure expansion microscopy (U-ExM) method.

About the speaker
Virginie Hamel (previously Hachet) is an expert in Cell Biology and Biochemistry. She completed her PhD under the supervision of Iain Mattaj at EMBL (Heidelberg, Germany, 2004) working on the role of importin alpha in nuclear envelope re-assembly in vitro using Xenopus laevis egg extracts. From 2005 to 2015, she worked as a post-doctoral fellow and then scientist collaborator in the laboratory of Prof. Gönczy at EPFL (Lausanne, Switzerland) where she first studied timing of mitotic entry in C. elegans embryos followed by dissecting the mechanisms of centriole assembly both in vitro and in vivo. Since 2015, she is co-heading the Centriole architecture lab with Prof Paul Guichard in the Molecular and Cellular Biology Department at the University of Geneva. Their lab focuses on deciphering the structural mechanisms governing centriole assembly combining the use of cell biology methods, in vitro reconstitution assays, cryo-microscopy/cryo-tomography and expansion microscopy.

Meet the speaker
To meet with the speaker informally after the talks, please contact administration@embl.fr. We especially encourage predocs and postdocs to take advantage of this opportunity.

Attachments
[Link to a file (for example a pdf of the seminar’s programme) - the file can be uploaded on the intranet]

Connection details
Zoom*: https://embl-org.zoom.us/j/95432724854?pwd=NnJvUWU5dzU0L1NheEM2SFlQM3FPQT09(Meeting ID: 954 3272 4854, Password: Passcode: 765338)

Please note that the talk will yes/not be recorded.
*For the FAQ section, as a zoom participant, please use either the chat function (the host will read out your question) or the “raise your hand” function and turn on your microphone.

About the speaker
Dr. Singh is a Senior Scientist in the Donald K. Johnson Eye Institute and Krembil Research Institute, located with University Health Network (UHN) since 2020. He is an Associate Professor in the Departments of Ophthalmology and Vision Sciences, and Laboratory Medicine and Pathobiology (LMP) at the Faculty of Medicine, University of Toronto. Prior to this, he was at McMaster University from 2012-2020 where he was a Scientist and Neural Program Lead at the Stem Cell and Cancer Research Institute, The David Braley Chair in Stem Cell Research, and an Associate Professor in the Department of Biochemistry and Biomedical Sciences at McMaster University. 

His lab utilizes mouse and patient-derived neural 3D organoid/assembloid models, in combination with multi-omic approaches, to study neurodevelopmental and adult neurological and vision disorders. His program focuses on studying genetic risk factors for neurological and vision disorders, and identifying molecular/cellular mechanisms of disease. The long-term goal is to utilize these platforms to study disease etiology, and develop regenerative medicine approaches such as genetic therapies.