Seminars & Events

Lipid phosphoinositides are master regulators of almost all aspects of a cell’s life and death and are generated by the tightly regulated activity of phosphoinositide kinases. Despite their critical roles in cell biology and frequent dysregulation in cancer, immune disorders, and neurodegeneration, the molecular mechanisms governing their activation, membrane recruitment, and regulation by binding partners have remained incompletely understood. I will describe our approach of using cryo-electron microscopy (cryo-EM), hydrogen-deuterium exchange mass spectrometry (HDX-MS), and membrane reconstitution assays to define how different phosphoinositide kinases are recruited and activated on cellular membranes. I will also describe our efforts to develop novel nanobody tools that can specifically block signalling inputs into phosphoinositide signalling as tools to study them in cellular models. Specifically, I will focus on two specific phosphoinositide kinase families, the first being the phosphatidylinositol 4 kinases and how they are recruited to the plasma membrane, and the second being the class I phosphoinositide kinases, with a focus on how they are misregulated in human disease. Together, these studies have uncovered shared principles and divergent strategies by which phosphoinositide kinases integrate multiple regulatory inputs to achieve precise spatiotemporal control of membrane recruitment and lipid kinase activity.

Please let me know if you would like to speak with John during his visit.

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

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

Abstract:
Actin in neuronal processes is both stable and dynamic. The origin & functional roles of the different pools of axonal actin is not well understood. We find that mutants that lack mitochondria along axons also lack dynamic actin in axons. Absence of axonal mitochondria and dynamic axonal actin regions does not markedly alter the Spectrin Membrane Periodic Skeleton in touch receptor neurons (TRNs). Restoring mitochondria cell autonomously in TRNs restores dynamic actin in a SOD-2 dependent manner. The dynamic actin regions are necessary and can bypass the requirement of axonal mitochondria for the localization of plasma membrane proteins in the TRNs and for the C. elegans touch escape response. Additionally, in the absence of axonal and synaptic mitochondria C. elegans habituate faster to localized gentle touch. Animals with dynamic axonal actin in the absence of mitochondria continue to habituate faster to localized touch stimulation, demonstrating an actin-independent role for mitochondria in habituation behaviours. We identify an in vivo mechanism by which axonal mitochondria locally facilitate actin dynamics through reactive oxygen species that we show is necessary for organization of electrical synapses & behaviour.

Abstract:
The lungs are continuously exposed to environmental challenges and require tightly regulated immune responses to maintain tissue homeostasis. Nociceptive sensory neurons, which detect noxious stimuli and communicate with immune cells through neuropeptides, are emerging as key regulators of lung immunity. While the sensory neuron–immune axis has been implicated in infections, allergy, and airway homeostasis, its role in cancer remains largely unexplored. In this talk, I will discuss the neuroimmune mechanisms that govern lung cancer progression and highlight how interactions between sensory neurons and immune cells shape the tumor microenvironment and antitumor immunity.

External attendees, if you wish to attend in person please contact Ana Ferreira@mrclmb.ac.uk

Abstract: The ability of antibodies to function inside cells has been well characterized in vitro and in mouse models, but the significance of intracellular neutralization in human cohorts has been challenging to determine. Rotavirus is a leading cause of severe gastroenteritis in young children, and we hypothesized that intracellular neutralization is an important mechanism of protection by rotavirus-specific antibodies. As antibodies in young infants are predominantly of maternal origin, we aimed to define how these maternal antibodies impact rotavirus vaccine efficacy. Using human infant samples from multiple rotavirus vaccine clinical trials, we tested whether intracellular neutralization correlates with protection. We found that maternal antibody levels, intracellular neutralization activity, and vaccine efficacy are tightly linked, helping explain the reduced vaccine performance seen in low- and middle-income countries. By defining the mechanisms that govern intracellular antibody-mediated protection, we aim to better understand vaccine responses in early life, and our ongoing work is informing the development of next-generation rotavirus vaccines.


External attendees, if you wish to attend in person please contact Leo James: lcj@mrclmb.ac.uk

2-3 July 2026

See website for further information https://www3.mrc-lmb.cam.ac.uk/sites/gsasymposium/

2-3 July 2026

See website for further information https://www3.mrc-lmb.cam.ac.uk/sites/gsasymposium/

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

Abstract:
To navigate towards an unknown food source, animals must accumulate evidence about the location of a goal and store this information in working memory. I will describe a microcircuit in the navigation center ofDrosophila whose connectivity and synaptic dynamics work together to support rapid formation of a stable working memory signal for goal direction. First, we identified a population of local neurons in the fan-shaped body called h∆K that exhibit a persistent bump of activity during odor-evoked striaght runs. Activity in this population correlates with goal-directed running, is required for pereistent running in response to odor, and can evoke reproducible goal-directed running when activated. To understand the mechanisms underlying this persistent activity, we examined both the connectivty of these local neurons and the dynamics of their synaptic inputs. h∆K neurons are tightly recurrently connected in a ring structure with a second group of neurons called PFG, and imaging from PFG neurons reveals similar persistent bump dynamics during odor-evoked straight runs. Using whole-cell recordings, we show that persistence in h∆K depends on recurrent signalling, and that h∆K receives slow recurrent excitation and fast inhibition from its synaptic partners. Computational modeling reveals that this combination of slow excitation with fast inhibition yields persistent attractor dynamics over a range of excitation and inhibition strengths. Finally, we show that despite their strong recurrent connectivity, h∆K and PFG show divergent dynamics during turns and rest. We can reproduce these differential dynamics in our model by using inhibition to dynamically uncouple activity in h∆K from PFG. When h∆K is inhibited, PFG neurons follow their inputs from the compass system; when h∆K is disinhibited, recurrent interactions lock this input into place, forming a heading memory. Consistent with this model, we find that inhibitory inputs onto h∆K increase during turns and are suppressed during odor input and goal-directed upwind runs. Together our work reveals a circuit and synaptic architecture that allows an ongoing measurement to be rapidly written to a recurrent circuit.

External attendees please arrive 10 minutes early to sign in at LMB Reception

The spliceosome, which catalyzes the removal of introns from pre-mRNA molecules, forms anew on each pre-mRNA intron, through a pathway involving multiple, successive assembly intermediates. Early spliceosome formation involves the binding of the U1 and U2 snRNPs to the 5′ and 3′ ends of an intron, respectively, yielding the A complex. Recruitment of the U4/U5.U6 tri-snRNP leads to the formation of the pre-B complex, which is remodeled into the B complex. The pre-B to B transition, and the transformation of the pre-catalytic B complex into an activated (Bact) spliceosome, involves extensive protein exchanges and RNA rearrangements that lead to the formation of a catalytically active U2/U6 structure. Our cryo-EM structures of pre-B, B and several distinct pre-Bact assembly intermediates, including one that was stalled by inhibiting the CDK11 kinase by OTS964, reveal an intricate cascade of highly coordinated structural changes during the activation phase of the human spliceosome. They also reveal unprecedented, large-scale translocations of proteins and entire RNP domains, with RNA helicases and kinases acting as driving forces.
Finally, while all hitherto published spliceosome structures have been determined using pre-mRNAs with relatively short introns (ca. 100-300 nts), we recently succeeded in reconstructing the cryo-EM structure of an activated (Bact) spliceosome that was assembled in vitro on a large (> 1kb) intron containing pre-mRNA. This structure reveals the mechanisms how the human spliceosome can dynamically adjust large (>30S) intron-hnRNP protein modules. Our studies also provide structural insights into the role of intron length for the assembly and catalytic activation of human spliceosomes

Register here: https://www.enterprise.cam.ac.uk/events/new-technologies-and-building-successful-biotechnology-companies-to-treat-disease/#harvey-lodish‑register

Celebrating his return to Cambridge and the MRC Laboratory of Molecular Biology (LMB), we are delighted to welcome Professor Harvey Lodish, Professor of Biology and Biological Engineering at MIT, who undertook his postdoctoral research at the LMB with Drs Sydney Brenner and Francis Crick, for a special lecture and discussion.

The event will explore how fundamental scientific discovery can be translated into real‑world benefit and the role universities play in supporting that journey with integrity, responsibility, and long‑term vision.

Professor Lodish will share insights from his academic career and his experience founding and advising biotechnology companies, including perspectives on mentorship, ethics, and the relationship between research excellence and enterprise. The lecture will be followed by a panel discussion, Q&A, and networking over lunch.

This unique opportunity is open to academics, postdoctoral researchers, and staff from across the Biomedical Campus, including the LMB, Clinical Schools, Milner Therapeutics Institute, and partner organisations

Schedule for the day:
10.00 – Arrival & coffee
10.30 – Welcome
10.45 – Special Lecture with Professor Harvey Lodish: New Technologies and Building Successful Biotechnology Companies to Treat Disease: A Personal History
11.45 – Panel & Q&A
12.30 – Lunch
13.30 – Event close

External attendees, if you would like to attend in person please contact Max Behzadi: mbehzadi@mrc-lmb.cam.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 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

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