Interviews and researchers’ testimonies from Biologists @ 100

During the Biologists @ 100 conference, we conducted and recorded interviews with a few researchers to get to know their work better, collecting their testimonies and feedback about the conference. At the end of the interview, researchers were asked to get their picture taken with a ‘polaroid frame’ and write a few keywords about their research. Some of these interviews are included in this report! As a cell biologist and microscopist, I was particularly interested and keen to learn more about organelle biology and cell division topics, and thus, I decided to interview and report on the work of these particular researchers. 

What is your most exciting result to date?

“I think my most exciting result was probably an accidental finding. I was doing some CLEM and I came across something in one of the images that I saw that could be a tube, and when we looked at it more closely it was a tunneling nanotube, so that was an amazing moment to find this structure, and to be able to image it!”

What was the highlight of this conference for you? 

“I would say the welcoming and encouraging atmosphere, particularly for ECRs. At the beginning of the conference, we had roundtable discussions with people from various fields who were willing to share their wisdom and talk about how they got where they are. Also, in most sessions, the ECRs were allowed to ask questions before the general audience, which is a very positive, encouraging, and welcoming atmosphere.”

An exciting talk describing intercellular mitochondrial transfer via tunneling nanotubes in response to mitochondrial import failure 

Protein import into mitochondria is essential for normal cellular function. Impaired import results in defective mitochondrial respiration and depletion of the major cellular ATP source, and is particularly damaging to cells with high energetic demands like neurons and cancer cells. Emily presented findings revealing that blocking import machinery has significant consequences on mitochondrial ultrastructure and dynamics, but unexpectedly little impact on import. Instead, using immunocytochemistry and confocal microscopy, Emily’s work uncovered an intriguing and novel rescue mechanism where cells with deficient mitochondrial import were observed to receive functional mitochondria from healthy cells via tunneling nanotubes (TNTs). Emily showed microscopy images revealing that TNTs contain microtubules and actin, which mediate the import of healthy mitochondria into the cell and discard those with blocked import sites. Emily and colleagues used live imaging and flow cytometry approaches to further characterize the transport of mitochondria through TNTs and the outcome of intercellular mitochondrial transfer: cells containing two populations of mitochondria. Her group is now interested in the fate of transferred mitochondria, whether they interact with acceptor cell mitochondria or are segregated, and what impact these donor mitochondria have on the acceptor cell. This work also raised an interesting question of whether other organelles, such as lysosomes and peroxisomes, could also be transported within TNTs, which will be further investigated. This discovery highlights a potential widespread intercellular strategy for maintaining mitochondrial functionality in multicellular organisms. 

Reference: Needs, H.I., Glover, E., Pereira, G.C. et al. Rescue of mitochondrial import failure by intercellular organellar transfer. Nat Commun 15, 988 (2024). https://doi.org/10.1038/s41467-024-45283-2.

What is your most exciting result to date?

“I am now able to generate cytoplasmic droplets of different sizes, and I can encapsulate them and form artificial cells that mimic real cells! Another interesting result is that depending on the level of organization of the cytoplasm, we observe a different speed of the cell cycle. If we only have microtubules, the cell cycle speed is very fast, but if we start adding components such as centrosomes, the cell cycle is also fast, but slows down over time. Adding even more components like nuclei and, thus, increasing the organization of the cytoplasm, makes the cell cycle even slower, and this is an interesting result to follow up and understand why this is happening!” 

What was the highlight of this conference for you?

“It’s nice to see so many people with many different backgrounds. What is particularly interesting is the focus on the environment and climate change. We know that this is happening, but for me, it is the first time I’m hearing real scientists talking about it, and it is also giving me more information and things that I didn’t know. I also liked the ECR session, it was a good opportunity to try to understand what I want to do in the future in my career.”

Cytoskeletal dynamics modulate cell cycle oscillations in frog egg extracts

The cell cycle represents a highly regulated biological oscillator, exemplified by the synchronous, 30-minute divisions observed in the early embryonic stages of the frog Xenopus laevis. These rapid cycles proceed without checkpoints or gap phases, driven by periodic cyclin B-Cdk1 activity, the core regulator of cell cycle progression. The use of Xenopus egg extracts as an in vitro system has revealed the molecular mechanisms underpinning these oscillations and the capacity of cellular structures to self-organize. Notably, microtubules and actin networks in these extracts spontaneously form dynamic architectures, including mitotic spindles and contractile networks, with spatial properties influenced by cell size. Encapsulation of cycling extracts into droplets of varying dimensions further reveals that cytoskeletal dynamics and cell cycle timing are sensitive to physical constraints. Martina’s recent work elucidates the role of cytoskeletal networks in modulating the speed of cell cycle oscillations using Xenopus egg extracts. Using cycling frog egg extracts, Martina monitored cytoskeletal and cell cycle dynamics, identifying periodic waves of actin contractions and microtubule aster (de)polymerization that persisted across multiple cycles. Quantitative analyses demonstrated that the presence of a microtubule aster significantly extended the cell cycle period, whereas periodic actomyosin contractions exhibited minimal impact on the oscillation timing. Therefore, Martina found that microtubule organization plays a pivotal role in modulating the tempo of cell cycle oscillations, interacting with the cytoplasmic regulatory network to influence cycle duration. This work highlights the critical interplay between dynamic cytoskeletal structures and biochemical networks in regulating cell cycle dynamics. It advances our understanding of how physical and molecular factors integrate to control cellular oscillatory behavior, offering new perspectives on the regulation of early embryonic divisions.

What is your most exciting result to date?

“We needed a tool in the lab to look better or more closely at how cells attach properly or improperly to the spindle, so we decided to generate tools in-house. We started to make antibodies recombinantly and to make antibodies against modifications of mitotic proteins. We now use these tools via live cell imaging or fixed cell analysis.” 

What was the highlight of this conference for you?

“Normally, we attend cell biology-specific meetings, and this is a very broad meeting, so we are excited, myself included, to look at topics outside of cell biology. In addition to that, there is a good technology talk at the end of this session, and I’m very interested in attending that.”

Development of Recombinant Antibodies for Investigating Dynamic Phosphorylation in Mitotic Processes

Traditional techniques, such as the use of fluorescent protein fusions (e.g., GFP), fail to capture real-time dynamics of protein post-translational modifications (PTMs) or conformational changes. These limitations hinder the understanding of critical cellular mechanisms, particularly during the highly dynamic process of mitosis. Keith’s work  focuses on understanding the mechanisms that control correct chromosome alignment and segregation. In particular, Keith is interested in a structure called the kinetochore, a large macromolecular protein complex built at the primary constriction of mitotic chromosomes that functions as an interface that directly binds to microtubules. To date, how kinetochores regulate attachments to microtubules and communicate their attachment status to the checkpoint remains incompletely understood. Keith’s recent work introduces elegant methodologies to tackle this problem by generating recombinant monoclonal antibodies and small antigen-binding fragments (scFvs) targeting phosphorylated epitopes in mitotic proteins. Using these tools, Keith and his group now have the means to investigate the spatiotemporal dynamics of kinetochore protein modifications and their roles in chromosome segregation and spindle checkpoint signaling. By generating scFvs against phosphorylated epitopes of Knl1 and Ndc80/Hec1, as well as a conformation-specific scFv for the active form of the spindle checkpoint protein Mad2, Keith’s team was able to map in real-time the phosphorylation dynamics at kinetochores during mitosis. Another exciting innovation from this methodology is the ability to directly visualize fluorescently-tagged versions of kinetochore proteins in live-cell contexts. Their findings highlight the role of phosphorylation in the initiation, maturation, and error correction of kinetochore-microtubule attachments. Additionally, Keith and his team elucidated mechanisms by which kinetochores communicate attachment status to the spindle assembly checkpoint, advancing our understanding of mitotic regulation. This work provides versatile tools for exploring protein dynamics in other cellular processes. Besides revealing critical insights into mitotic phosphorylation events, these tools could potentially be applied for broader use in cell biology research. For example, extending these methods to other PTMs and protein conformational changes could further elucidate the dynamics of other regulation mechanisms in live-cell studies.

Reference: DeLuca K.F. et al., Generation and diversification of recombinant monoclonal antibodies. Elife 10:e72093 (2021). doi: 10.7554/eLife.72093.

Georgia Hulmes, Postdoctoral Research Associate at The University of Manchester

Pre-mitotic cell geometry predictably defines the symmetry of post-mitotic organelle inheritance.

Georgia presented her recent findings on the role of cell morphology in regulating division dynamics and cellular outcomes. Traditionally, mitotic rounding has been regarded as a hallmark of eukaryotic cell division, promoting the fidelity of chromosome segregation and symmetric distribution of cellular components. However, Georgia and her colleagues’ recent work introduces an alternative paradigm—”isomorphic division”—observed in mesenchymal-like cells within complex tissue environments. One of the key highlights of the research is the discovery that mesenchymal-like cells can bypass the mitotic rounding process under specific in vivo conditions, retaining the cell’s interphase morphology throughout mitosis. By combining zebrafish as an in vivo model and in vitro micropatterning tools, Georgia and her team demonstrated that interphase cell geometry can reliably predict post-mitotic outcomes. Georgia’s results show that organelles such as endosomes, mitochondria, and the Golgi apparatus exhibit geometry-driven inheritance patterns and reveal that morphology-induced asymmetry in organelle distribution directly affects the functional state of daughter cells. In this study, researchers combined live imaging to enable detailed observation of cell division dynamics in vivo in zebrafish with micropatterning tools to generate precise cell geometries in vitro to control and analyze division behavior. This work provides relevant insight into the relationship between cell shape, organelle inheritance, and cellular fate. In the future, these findings could be applied to other cellular/tissue contexts where asymmetric division also plays a pivotal role.

Reference: Holly E. Lovegrove et al., Interphase cell morphology defines the mode, symmetry, and outcome of mitosis. Science 388, eadu9628 (2025). doi:10.1126/science.adu9628

What was your most exciting result to date?

“My most exciting result was when I found that integrins and hydrostatic pressure are regulated by YAP/TAZ!”

What was the biggest highlight of this conference for you?

“As a final year Ph.D. student, I quite liked the ECR session where we could talk with people from different professions and taking different career routes, and that helped me to think about what I should do in the future and what I should be prepared for my career path”.

The ageing niche: Does the Hippo control it all?

​​Aging involves structural changes in tissues and declines in function, driven by biochemical and mechanical alterations in the extracellular matrix (ECM) that impair cellular mechanotransduction. These changes disrupt communication, homeostasis, and regeneration. Notably, systemic interventions can sometimes reverse aging phenotypes, offering insights into tissue repair. The Hippo pathway, a mechanotransduction pathway with key regulators YAP and TAZ, plays crucial roles in proliferation and healing but is often dysregulated in aged tissues. However, the mechanisms by which YAP/TAZ influences cellular responses in aging remain unclear. Nancy is keen on understanding how and why cells respond to mechanical stress in an aging environment. To do this, Nancy employed an isogenic library of HEK293A cells with knockouts of core Hippo pathway components, alongside fibroblasts derived from spiny mice, which are insensitive to stiffness and can regenerate without scarring, and wild-type mice. Using digital holographic microscopy, a label-free quantitative phase imaging method, Nancy assessed cellular morphological changes under mechanical stimuli mimicking aging environments, including varying ECM stiffness, hydrostatic pressure, and specific ECM substrates. Nancy’s exciting preliminary findings reveal that YAP/TAZ regulates integrin-engaging substrates in mediating cellular volume changes in response to stiffness and hydrostatic pressure. These results highlight the mechanistic interplay between the Hippo pathway and extracellular mechanical cues in shaping cellular behavior within aged niches. This study reveals the role of the Hippo pathway in cellular responses to mechanical stimuli and provides insight into the mechanotransductive processes underlying aging.

Nawseen Tarannum – University of Manchester

Mitotic spindle orientation and dynamics are fine-tuned by anisotropic tissue stretch via NuMA localization.

​​Cells constantly encounter mechanical forces from their tissue environment, which they must sense and respond to for proper tissue formation and maintenance. Errors in these processes can lead to developmental defects and diseases like cancer. One key function influenced by such forces is the orientation of cell division, determined by mitotic spindle positioning. While tissue stretching aligns divisions along the stretch axis, it remains unclear whether this mechanosensitivity arises directly from force or indirectly via changes in cell shape. To address this, Nawseen employed the embryonic animal cap tissue of the frog Xenopus laevis, which allows the application of reproducible external tensile forces, to investigate the regulation of mechanosensitive division orientation. Nawseen has focused specifically on the role of NuMA (nuclear mitotic apparatus protein), a key component of the spindle orientation machinery, in the regulation of mechanosensitive spindle orientation. Nawseen demonstrated that cortical localization of NuMA is dynamic and sensitive to tissue stretch, with recruitment to the polar cortex earlier during mitosis in stretched tissues. Nawseen also showed that this cortical recruitment of NuMA coincides with the onset and ensuing stretch-induced amplification of spindle oscillations. Nawseen further revealed that spindle oscillations are reduced upon knockdown of NuMA, and that reduced NuMA impairs the alignment of cell divisions to stretch and cell shape. Nawseen’s recent work indicates that cells align divisions to cell shape under tissue stretch and that this process involves a direct response to force via NuMA localization, rather than an indirect response to force via cell shape changes. By integrating live tissue imaging with mathematical modeling, Nawseen’s latest research establishes that NuMA fine-tunes spindle dynamics, mediating the precise alignment of cell divisions with cell shape and anisotropic tension. These results provide insight into the mechanisms by which mechanical forces regulate cellular behaviors and contribute to tissue organization.

Reference: Tarannum N. et al., Mitotic spindle orientation and dynamics are fine-tuned by anisotropic tension via NuMA localisation. bioRxiv 2024.10.17.617436; doi: https://doi.org/10.1101/2024.10.17.617436.

Biologists @ 100 was more than just a conference

Biologists @ 100 was a vibrant celebration of global collaboration, multidisciplinary innovation, and an engaging conference for researchers at all career stages. As a conference reporter for FocalPlane, I had the unique opportunity to interview researchers, which I had never done before. I was also given the chance to bring my ideas and together with the preLights? and the Node community members, we came up with the ‘polaroid frame’ pictures taken at the conference. I believe that this made the conference more engaging and memorable. May The Company of Biologists continue to support, inspire and shape the future of biology for the next 100 years!

To read more about the highlights from Biologists @ 100, read part one of my conference report: https://focalplane.biologists.com/2025/05/08/biologists-100-conference-report/

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