Related talks@cam

Abstract: High fidelity passing on of genetic material is essential to reproduction. Typically, this is accomplished by primordial germ cells (PGCs), which eventually produce sperm or eggs. In most animals, PGCs are specified far from the future gonads and must migrate through developing tissues to reach them. Failure to complete this journey can result in infertility or extra-gonadal germ cell tumours. Despite this important biomedical relevance, very little is known about PGC migration in mammalian embryos. Here, we performed dynamic and in-depth analyses of PGC migration during mouse embryogenesis, encompassing historically inaccessible stages. We found that migrating PGCs extend dynamic actin-rich protrusions, indicative of a migration strategy distinct to that used in non-mammalian model organisms. Their protrusive migration enables them to navigate through ECM barriers and increasingly developed tissues. These morphogenetic changes around PGCs impose increasing physical confinement, leading to significant nuclear deformation and even cell rupture. Endogenous and artificial increases in confinement lead to an increased incidence of DNA damage in PGCs, but not somatic cells. As a possible adaptation to mitigate this surprising stress, we found that PGCs deplete their nuclear lamina and have highly wrinkled nuclear envelopes that may enable them to squeeze through confined spaces damage-free. Overall, our insights into the fascinating journey of PGCs during mouse embryogenesis raise important questions about DNA repair, nuclear adaptations, and genome integrity in the mammalian germline.

Miguel Ángel Ortiz Salazar Title: Endogenous Nodal diverts Wnt signaling interpretation from posterior mesoderm to definitive endoderm in geometrically constrained human pluripotent cells.

Abstract: The ligands FGF8 and WNT3A are crucial for embryonic development. They are involved in cell migration, aid mesoderm induction early at gastrulation, and fuel axial elongation by generating Neuromesodermal progenitors (NMPs) that pattern posterior cell fates in the embryo. While both events have been extensively studied, the mechanisms by which these signals produce different outcomes depending on the context remain elusive. Here, we studied how the Wnt signaling dynamics correlate with their cell fate.

When human embryonic stem cells are exposed to these signals under standard culture conditions, they indeed induce an NMP -like state. In contrast, however, when the same protocol is performed in geometrically constrained colonies, an intricate 3D structure emerges, featuring a ball of epiblast disk-like cells (SOX2+, OCT4 , NANOG , ECAD ) on top of layers of definitive endoderm (DE) (SOX17, FOXA2 , GATA6 , NCAD , OTX2 ). When these structures are exposed to increasing WNT doses, signaling levels as measured with live GFP ::ß-catenin are elevated. However, these elevated WNT signals do not induce mesoderm or posteriorize the responding cells, challenging the classic concentration-dependent morphogen mechanism. By manipulating signaling pathways, we found that DE differentiation results from elevated endogenous NODAL signaling together with the exogenous WNT stimulation. The ability of WNT to induce NMPs and their specialized descendants, pre-somitic mesoderm (PSM) or neural progenitors (CDX1+, CDX2 , and TBX6 or SOX1 , SOX2 ) is restored only when WNT activation is combined with NODAL inhibition. Furthermore, combining live NODAL dynamics with time-point inhibitions, revealed that allowing NODAL signaling for the first 24 hours, enhances PSM induction while allowing it for 48 hours induces both DE and PSM fates. This shows that NODAL changes how the WNT signal is interpreted and is the main determinant of whether cells differentiate to endoderm or mesoderm. Finally, we determined that CHIR , a commonly used chemical Wnt activator, can induce PSM in a concentration-dependent manner with qualitatively different signaling dynamics through both the WNT and NODAL pathways compared to stimulation with WNT3A ligand.

Collectively, we demonstrate that cell fate decision-making is determined by the interplay between multiple pathways and not only by the levels of a single pathway, highlighting the dynamic nature of development.

This work has been funded by the National Science Foundation (MCB-2135296), Rice University, and Consejo Nacional de Ciencia y Tecnología (CONACYT – 41944)

Speaker: Katie Goodwin-MRC LMB; Miguel Ángel Ortiz Salazar-MRC LMB
Monday 19 May 2025, 14:30-15:30
Venue: In person at Gurdon Institute and Online.
Series: Morphogenesis Seminar Series; organiser: Jia CHEN.

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Tue 27 May 14:30: Scaling life: How Single Cells Orchestrate Tissue-Level Coordination TUESDAY online seminar (details will be sent via email to subscription list)

Wed, 16/04/2025 - 11:17

Scaling life: How Single Cells Orchestrate Tissue-Level Coordination

Abstract: 

Morphogenesis relies on the precise coordination of single-cell behaviors to build complex tissues. Intestinal development exemplifies this process, as crypt formation emerges from tightly regulated biochemical and mechanical cues. Using organoid models combined with in vivo studies, we dissect how crypt morphogenesis is initiated by actomyosin-driven apical constriction and accelerated by osmotic forces. We identify a critical mechanochemical feedback loop mediated by calcium-dependent cytosolic phospholipase A2 (cPLA2), which senses mechano-osmotic changes and triggers robust crypt formation via arachidonic acid production and myosin relocalization. Together, our work reveals how cells integrate mechanical and osmotic signals to orchestrate irreversible tissue-scale transformations during development.

TUESDAY online seminar (details will be sent via email to subscription list)

Speaker: Prisca Liberali, FMI
Tuesday 27 May 2025, 14:30-15:30
Venue: Online (Tuesday!).
Series: Morphogenesis Seminar Series; organiser: Jia CHEN.

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Mon 12 May 14:30: Title to be confirmed

Wed, 16/04/2025 - 10:31

Title to be confirmed

Abstract not available

Speaker: Kaelyn Sumigray, Department of Genetics at Yale School of Medicine
Monday 12 May 2025, 14:30-15:30
Venue: Online.
Series: Morphogenesis Seminar Series; organiser: Jia CHEN.

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Mon 02 Jun 14:30: Maik Christian Bischoff-Plexin/Semaphorin Antagonism Orchestrates Collective Cell Migration and Organ Sculpting by Regulating Epithelial-Mesenchymal Balance

Wed, 16/04/2025 - 10:29

Maik Christian Bischoff-Plexin/Semaphorin Antagonism Orchestrates Collective Cell Migration and Organ Sculpting by Regulating Epithelial-Mesenchymal Balance

Maik Christian Bischoff

Title:

Plexin/Semaphorin Antagonism Orchestrates Collective Cell Migration and Organ Sculpting by Regulating Epithelial-Mesenchymal Balance

Abstract

Cell behavior emerges from the intracellular distribution of properties like protrusion, contractility, and adhesion. Thus, characteristic emergent rules of collective migration can arise from cell-cell contacts locally tweaking architecture, orchestrating self-regulation during development, wound healing, and cancer progression. The Drosophila testis-nascent-myotube-system allows dissection of contact-dependent migration in vivo at high resolution. Here, we describe a role for the axon guidance factor Plexin A in collective cell migration: maintaining cell-cell interfaces at a precise point on the epithelial-mesenchymal spectrum. This is crucial for testis myotubes to migrate as a continuous sheet, allowing normal sculpting-morphogenesis. Cells must maintain filopodial N-cadherin-based junctions and remain ECM -tethered near cell-cell contacts to spread while collectively moving. Our data further suggest Semaphorin 1b is a Plexin A antagonist, fine-tuning activation. This reveals a contact-dependent mechanism to maintain sheet-integrity during migration, driving organ-morphogenesis. This is relevant for mesenchymal organ-sculpting in other migratory contexts like angiogenesis.

Speaker: Maik Christian Bischoff, UNC, Mark Peifer lab; Harry McNamara
Monday 02 June 2025, 14:30-15:30
Venue: Online.
Series: Morphogenesis Seminar Series; organiser: Jia CHEN.

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Mon 28 Apr 19:30: Malaria Mosquito Genomics Across Africa

Tue, 15/04/2025 - 10:29

Malaria Mosquito Genomics Across Africa

Malaria is a preventable treatable infectious disease but still it kills up to 600,000 people each year, primarily children under the age of five. The disease is caused by a single celled parasitic organism that is only transmitted between humans by Anopheles mosquitoes. If the mosquitoes that transmit the parasite were eliminated or prevented from transmitting, malaria would end. Gaining a deeper understanding of Anopheles malaria mosquitoes is an especially important undertaking in Africa, where the vast majority of malaria deaths occur and where there are many species contributing to the disease burden. Among these, four are considered major malaria vectors, probably accounting for more than 95% of transmission. This talk will present several different genomic approaches we are taking to thoroughly characterise Anopheles mosquitoes. These include amplicon panels to understand mosquito species diversity and distributions, short read sequencing to glean a comprehensive understanding of population structure and selection, and long read sequencing to peek into rapidly diverging regions of the genome that short reads cannot offer resolution for. This talk will discuss what we have learned to date and how this contributes to malaria control.

More details here.

Speaker: Dr Mara Lawniczak, Senior Group Leader, Wellcome Sanger Institute
Monday 28 April 2025, 19:30-21:00
Venue: Location: Wolfson Lecture Theatre, Churchill College, and Zoom.
Series: Cambridge Society for the Application of Research (CSAR); organiser: John Cook.

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Mon 12 May 19:30: Bioelectronic Medicine

Tue, 15/04/2025 - 10:28

Bioelectronic Medicine

Neurological conditions affect one in six people, imposing significant health, economic and societal burden. Bioelectronic medicine aims to restore or replace neurological function with the help of implantable electronic devices. Unfortunately, significant technological limitations prohibit these devices from reaching patients at scale, as implants are bulky, require invasive implantation procedures, elicit a pronounced foreign body response, and show poor treatment specificity and off-target effects. Over the past decade, novel materials and fabrication methods inspired from the microelectronics industry have been shown to overcome these limitations. Recent literature provides powerful demonstrations of thin film implants that are miniaturised, ultra-conformal, stretchable, multiplexed, integrated with different sensors and actuators, bioresorbable, and minimally invasive. This talk discuss the state-of-the-art of these new technologies and the barriers than need to be overcome to reach patients at scale.

More details here.

Speaker: Professor George Malliaras FRS, Prince Philip Professor of Technology, Department of Engineering, Cambridge University
Monday 12 May 2025, 19:30-21:00
Venue: Location: Wolfson Lecture Theatre, Churchill College, and Zoom.
Series: Cambridge Society for the Application of Research (CSAR); organiser: John Cook.

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Mon 12 May 19:30: Bioelectronic Medicine

Fri, 11/04/2025 - 12:55

Bioelectronic Medicine

Neurological conditions affect one in six people, imposing significant health, economic and societal burden. Bioelectronic medicine aims to restore or replace neurological function with the help of implantable electronic devices. Unfortunately, significant technological limitations prohibit these devices from reaching patients at scale, as implants are bulky, require invasive implantation procedures, elicit a pronounced foreign body response, and show poor treatment specificity and off-target effects. Over the past decade, novel materials and fabrication methods inspired from the microelectronics industry have been shown to overcome these limitations. Recent literature provides powerful demonstrations of thin film implants that are miniaturised, ultra-conformal, stretchable, multiplexed, integrated with different sensors and actuators, bioresorbable, and minimally invasive. This talk discuss the state-of-the-art of these new technologies and the barriers than need to be overcome to reach patients at scale.

More details here.

Speaker: Professor George Malliaras FRS, Prince Philip Professor of Technology, Department of Engineering, Cambridge University
Monday 12 May 2025, 19:30-21:00
Venue: Location: Wolfson Lecture Theatre, Churchill College, and Zoom.
Series: Cambridge Society for the Application of Research (CSAR); organiser: John Cook.

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Mon 16 Jun 19:30: An Introduction to The Alan Turing Institute, the National Institute for Data Science, and Artificial Intelligence

Fri, 11/04/2025 - 12:50

An Introduction to The Alan Turing Institute, the National Institute for Data Science, and Artificial Intelligence

The Alan Turing Institute was established ten years ago and, in this time, it has delivered a number of worlds firsts such as the first 3D printed stainless steel pedestrian bridge, a digital twin of the United Kingdom’s air space, digital twins of cardiac systems in patients, as well as the research vessel the Sir David Attenborough. This talk will focus on some of the achievements of the institute and describe the Grand Challenges it has defined to address contemporary societal issues we face globally namely in the Environment and Sustainability, Defence and Security, and Health and Medicine.

More details here.

Speaker: Professor Mark Girolami, Chief Scientist, The Alan Turing Institute; RAE Research Chair in Data Centric Engineering, Cambridge University Engineering Department
Monday 16 June 2025, 19:30-21:00
Venue: Location: Wolfson Lecture Theatre, Churchill College, and Zoom.
Series: Cambridge Society for the Application of Research (CSAR); organiser: John Cook.

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