Seminars & Events

External attendees, if you would like to attend in person please contact Max Behzadi: mbehzadi@mrclmb.ac.uk

This will be a joint seminar, please see both abstracts below.

Delphine’s Abstract:
Two-pore domain potassium channels regulate neuronal excitability through hyperpolarizing leak currents and play important roles in sensory physiology. Among them, THIK1 and THIK2 remain poorly characterized despite their strong enrichment in nociceptive dorsal root ganglion (DRG) neurons. In this seminar, we will present a multidisciplinary study combining molecular analyses, electrophysiology, and behavioral approaches to investigate the contribution of THIK channels to sensory neuron excitability and pain processing under physiological and inflammatory conditions. THIK1 and THIK2 expression patterns were characterized in mouse DRG, while whole-cell recordings and behavioral analyses were used to explore the consequences of THIK deletion on neuronal function and nociceptive responses. Our findings reveal an unexpected role for THIK channels in the regulation of sensory neuron activity and thermal pain sensitivity, highlighting these poorly understood K2P channels as potential new players in inflammatory pain mechanisms and possible therapeutic targets for chronic pain disorders.

Franck’s Abstract:
Despite being the first channel in the K2P family to be cloned, TWIK1 remains largely mysterious in terms of its physiological role. We have shown that its sensitivity to extracellular pH is accompanied by a change in its ionic selectivity, thereby reinforcing questions about its function. At neutral physiological pH, TWIK1 is, like most potassium channels, selective for K+ ions. However, when exposed to a pH below 6—as occurs in the recycling endosomes it transits during intracellular trafficking—the channel undergoes conformational changes. These changes alter the structure of its selectivity filter, rendering TWIK1 permeable to Na+ ions. We have identified the molecular determinants responsible for this pH sensitivity and proposed a model describing the sequence of molecular events occurring around the selectivity filter during the gradual acidification of the extracellular environment. Research into the physiological role of this dynamic selectivity suggests that, in certain functional contexts, TWIK1’s preference for potassium ions may not be absolute, nor even indispensable.

An informal one day meeting organised by MRC LMB, MRC LMS and Imperial College London examining the application of cutting edge biophysical techniques in complex biological settings. Bringing together scientists in both academia and industry for stimulating talks and discussions how these new and emerging technologies may be able to address challenging questions in the future.

For more information see https://www3.mrc-lmb.cam.ac.uk/sites/nextgen/

External attendees, if you would like to attend in person please contact Max Behzadi: mbehzadi@mrclmb.ac.uk

Abstract:
Learning is essential for survival. Evidence suggests that memories are formed through changes in protein expression or localisation in specific brain regions. Our goal is to map the full complement of protein changes that occur during learning, in distinct subcellular compartments, within specific brain cells. To achieve this, we use proximity labelling to identify proteins that are dynamically regulated during learning within the experimentally accessible Caenorhabditis elegans (worm) brain. Our data demonstrate that this strategy efficiently labels known regulators of learning and memory, including components of cAMP, MAPK, and G protein signalling, and proteins involved in synaptic vesicle exocytosis. We have also discovered novel regulators of learning, including ligand-gated ion channels, as well as proteins involved in fatty acid metabolism and protein quality control. Using a similar strategy, we have begun mapping learning-associated protein changes at synapses and have uncovered additional candidate regulators. Together, these findings establish proximity labelling as a powerful approach for defining the molecular mechanisms of learning, with broad potential for application to other organisms and behaviours.

Leo James: lcj@mrclmb.ac.uk

Abstract: Protein aggregates compromise cellular homeostasis, and their accumulation is associated with neurodegeneration. The selective removal of these aggregates, termed aggrephagy, involves the cargo receptors p62, NBR1, and TAX1BP1, which cooperate to sequester the cargo within nascent autophagosomes. Importantly, protein aggregates resist degradation in various diseases despite being recognized by p62, suggesting that certain aggregates can evade aggrephagy initiation. To investigate how aggrephagy initiation is regulated and how protein aggregates escape autophagic degradation, we combined cellular approaches with biochemical reconstitution. We identified TAX1BP1 as a critical regulator of aggrephagy initiation and Tau aggregate clearance. TAX1BP1 recruits upstream autophagy factors, including the ULK1 complex and the kinase TBK1, to the cargo, thereby promoting autophagosome biogenesis.

External attendees, if you wish to attend in person please contact Tanmay Bharat: tbharat@mrc-lmb.cam.ac.uk

Abstract to follow

External attendees, if you would like to attend in person please contact David Favara: dfavara@mrc-lmb.cam.ac.uk

Adhesion GPCRs are among the most intriguing unresolved problems in receptor biology. The key challenge for their understanding is to decipher their input-output relationship. Their unusual architecture and sensitivity to mechanical and adhesive inputs raise a central question: how are extracellular cues converted into defined signalling outputs? Unlike classical GPCRs, they do not merely bind soluble ligands but instead sense and interpret mechanical stimuli through an elaborate molecular architecture built around the GAIN domain and a cryptic intramolecular agonist. I will present recent work that brings this problem into quantitative focus through through a combination of biophysical measurements and method development: tools for acute, time-controlled receptor activation, strategies for engineered ligand engagement, and force-resolved assays that capture GAIN-domain unfolding, receptor dissociation and mechanochemical signalling. Together, these approaches reveal how adhesion GPCRs convert mechanical and adhesive information into distinct downstream responses. This emerging framework recasts adhesion GPCRs as measurable signalling machines and opens a route towards understanding their roles in neural development, tissue organisation, immunity and cancer with molecular precision.

The seventeenth annual LMB-CamAWiSE event!

Are you wondering how best to utilise your scientific skills?
Are you planning your next step in academia or considering pursuing a career away from the bench?
Would you like more information about different scientific careers from a diverse range of speakers?
Then join us to hear from three inspirational speakers who have gone on to do a variety of roles using their scientific knowledge, skills and expertise, the common thread being they have all spent time at the MRC Laboratory of Molecular Biology in Cambridge. We welcome them back to hear about their career paths, and to be inspired by what they have achieved.
This event is run in collaboration with CamAWiSE – Connecting and Inspiring Women in Science, Technology, Engineering, Mathematics and Medicine.
ALL are welcome to attend!
Speakers:
Louise Fets, Group Leader, MRC Laboratory of Medical Sciences
Carly Dix, Associate Director, AstraZeneca
Rihab Gam, Head of Biology, Elastin Biosciences
This event is free and open to all within and outside of the LMB.

Abstract: TBC

Abstract to follow.

External attendees, if you would like to attend, please contact Tanmay Bharat: tbharat@mrclmb.ac.uk

https://mrc-lmb-cam-ac-uk.zoom.us/j/94514662338?pwd=QFmpzVDjmvrrMmV476z2wynx6r2aoA.1