Doing great science depends on teamwork, whether this is within the lab or in collaboration with other labs. However, sometimes the resources that support our work can be overlooked. Our ‘Featured resource’ series aims to shine a light on these unsung heroes of the science world. In our latest article, we hear from Denis Bienroth, who describes the work of VR-Omics.

What is VR-Omics?

VR-Omics is a computational framework that analyses, visualises, explores, and interprets spatially resolved transcriptomics (SRT) data. It supports SRT data from various technologies, including sequencing-based and imaging-based platforms. Notably, VR-Omics is the first tool to analyse and visualise SRT data in both 2D desktop and virtual reality (VR) environments. It incorporates an automated workflow for data preprocessing and spatial mining. Additionally, VR-Omics is available at our VR-Omics Website. It is an open-source software, ensuring accessibility for all users. This platform is highly valuable for researchers as it also facilitates cross-platform comparisons, particularly when deploying different SRT technologies.

The VR-Omics Introduction Video showcases a comprehensive array of SRT Methods, providing an overview of all the options available.

What inspired VR-Omics’ development and its target challenges?

The development of VR-Omics was inspired by the realisation that existing tools for spatially resolved transcriptomics (SRT) data analysis required a high level of computational knowledge, making them inaccessible to many biologists. We aimed to create a solution that empowers researchers by providing a user-friendly graphical user interface (GUI) and eliminating the need for extensive computational expertise. VR-Omics puts the power back in the hands of biologists, allowing them to easily work with their own data and explore the fascinating world of gene expression landscapes.

Which SRT methods are currently supported?

VR-Omics currently supports a variety of spatially resolved transcriptomics (SRT) methods, including both sequencing-based and imaging-based technologies. The supported sequencing-based SRT methods include Visium from 10X Genomics, Tomo-seq, and STOmics from BGI. In terms of imaging-based SRT methods, VR-Omics supports Xenium from 10X Genomics and MERFISH from Vizgen. Additionally, VR-Omics allows for the analysis of custom SRT data, providing flexibility for users who are using their own spatial transcriptomics data not suitable with any of the aforementioned vendors. It’s worth mentioning that CosMx by Nanostring will also be available in VR-Omics shortly, further expanding the range of supported SRT methods. The wide range of supported SRT methods in VR-Omics ensures its compatibility with diverse experimental setups, enabling researchers to analyse and visualise their spatial data effectively.

How can biologists’ access and utilise VR-Omics for their research?

VR-Omics empowers biologists to improve their research and make significant findings by providing an immersive and intuitive platform for spatially resolved transcriptomics (SRT) data analysis. Its visualisation capabilities enable a deeper understanding of gene expression landscapes, while cross-platform compatibility facilitates collaboration and data comparison. By streamlining workflows and eliminating computational complexities, VR-Omics allows researchers to focus on interpreting their data and uncovering valuable insights, ultimately accelerating scientific progress in diverse fields. VR-Omics is available at our VR-Omics Website.

Can I use VR-Omics with my own data?

Absolutely! VR-Omics is specifically designed to empower you to use your own data. It seamlessly supports spatially resolved transcriptomics (SRT) data generated through sequencing-based or imaging-based technologies, ensuring compatibility with multiple SRT platforms. Once loaded, VR-Omics streamlines the analysis process with its integrated workflow, automating tasks such as clustering, filtering, and spatial variable gene analysis. This means you can effortlessly explore and gain valuable insights from your data.

Can I export my findings to share them with my colleagues?

VR-Omics provides convenient export options for sharing your findings. You can export the output of the automated workflow, including plots, CSV files, and HDF files for downstream analysis. Additionally, the software allows you to export data directly from the Visualiser, such as gene lists, selected Regions of Interest (ROIs), screenshots, and videos. These versatile export capabilities enable you to easily share your results and collaborate effectively with your colleagues.

How can I explore my spatial data with VR-Omics?

With VR-Omics’ Visualiser feature, you can explore your spatial data on your desktop or in an immersive virtual reality (VR) environment. It supports side-by-side gene comparisons, merging gene expression patterns in one slide, and overlaying 3D objects for improved orientation. The Figure Viewer allows real-time interaction with output plots. VR-Omics offers a range of powerful tools to enhance your exploration and analysis of spatial data.

What if I don’t know how to process my data? Do I need computational knowledge to run VR-Omics?

Not at all! VR-Omics is designed to be user-friendly and accessible, even for those without extensive computational knowledge. Its integrated workflow automates essential processing steps, allowing you to analyse your data without requiring deep computational expertise. With VR-Omics, you can easily load your data and navigate the intuitive graphical user interface (GUI) for seamless data processing and analysis. It empowers biologists to explore and interpret their spatial transcriptomics data effortlessly, regardless of their computational background.

Can VR-Omics facilitate the creation and exploration of 3D spatial data?

Certainly! VR-Omics is specifically designed to facilitate the creation and exploration of 3D spatial data. While many platforms are limited to visualising individual sections from a single spatially resolved transcriptomics (SRT) experiment, VR-Omics takes it a step further. It enables you to seamlessly navigate through multiple sections, such as serial sections of the same tissue, for a more comprehensive understanding of spatial gene expression patterns in three-dimensional space. With the immersive capabilities of virtual reality (VR), VR-Omics provides an enhanced environment to study complex biological systems and unravel intricate spatial relationships. It empowers researchers to delve into the three-dimensional landscape of their SRT data, gaining deeper insights into the biology of the system under study.

What are the next plans and features for VR-Omics?

The future of VR-Omics is driven by our commitment to constant improvement and expanding its capabilities. Our plans include incorporating new spatially resolved transcriptomics (SRT) methods, such as Nanostring (CosMx), to broaden the range of compatible technologies. We are dedicated to staying up to date with the latest algorithms and packages used in the literature, ensuring that the Automated Workflow remains robust and relevant. Additionally, we are excited to introduce new features, to enhance the user experience and analysis possibilities. Our goal is to continuously evolve VR-Omics, incorporating user feedback and advancements in the field, to provide a cutting-edge software solution for spatial data analysis.

What are the benefits of using VR for spatial data work, and can I use VR-Omics without VR?

VR-Omics offers the flexibility to work with or without VR hardware, allowing users to choose their preferred mode of interaction. While VR provides an immersive experience for spatial data exploration, the benefits go beyond visualisation. In a virtual reality environment, users can effectively navigate and analyse complex 3D spatial structures, revealing hidden patterns, identifying spatial co-expression relationships, and gaining new insights into biological phenomena. However, even without VR, VR-Omics provides powerful analysis and visualisation tools, ensuring that users can effectively analyse and interpret spatial data. Whether in VR or non-VR mode, VR-Omics empowers researchers to unlock the full potential of their spatial data.

What if a necessary feature is missing in VR-Omics Visualiser or the Automated Workflow that would benefit my project?

We highly value user feedback and are dedicated to continuously improving VR-Omics based on the needs of our users, particularly biologists working with spatial data. If you find that there is a missing feature or a step in the Automated Workflow that would benefit your project, we are always eager to hear your suggestions. We actively seek input from users and encourage collaboration to enhance the software’s functionality. By engaging with the community, we aim to incorporate new features and improvements that address the specific requirements of our users. Your input is invaluable, and we are committed to making VR-Omics a powerful and user-friendly tool for spatial data analysis.

What if I have any questions, is VR-Omics documented and supported?

If you have any questions or need assistance while using VR-Omics, you can rely on its Documentation and support resources. VR-Omics is well-documented, providing detailed guides, tutorials, and documentation that explain its features and functionality. Additionally, the VR-Omics team is available to help address any queries or issues you may encounter. They are committed to providing support and ensuring a smooth user experience with the software. Shot us an email (denis.bienroth@mcri.edu.au) if you have any questions or inquiries.

References

1: Asp, M. et al. A Spatiotemporal Organ-Wide Gene Expression and Cell Atlas of the Developing Human Heart. Cell 179, (2019).

2: Vizgen Data Release V1.0. May 2021, https://info.vizgen.com/mouse-brain-data

3: 10X Genomics resources, Mouse Brain Coronal Section 1(FFPE), https://www.10xgenomics.com/resources/datasets/mouse-brain-coronal-section-1-ffpe-2-standard

4: Junker, J. P. et al. Genome-wide RNA Tomography in the Zebrafish Embryo. Cell, 662–675 (2014).

5: High resolution mapping of the breast cancer tumour microenvironment using integrated single cell, spatial and in situ analysis of FFPE tissue, https://www.10xgenomics.com/products/xenium-in-situ/preview-dataset-human-breast

(3 votes)

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We are happy to announce the 2nd edition of the EMBO workshop “The Evolution of Animal Genomes”.

The event will take place in Seville (Spain), from 18-21 September 2023 (Registration and abstract deadline: 12th July 2023)

Genome evolution represents the basis of species adaptation to changing environments and habitats. Recent breakthroughs in sequencing technologies resulted in the acquisition of complete genome information for an increasing number of animal species, propelling the field of evolutionary genomics into a new era of discovery. Yet, our limited capacity to interpret genome variation hinders our understanding on how phenotypical changes drive adaptation. This urges the development of novel strategies to reconcile genomic sequence and function, for which a proper integration of cell-specific gene programs, non-coding regulation and 3D chromatin organization becomes essential. Further, establishing causal relationships between genome mutations and phenotypes still remains a major challenge in the field. Within this context, novel synthetic biology approaches are emerging as a means to understand developmental processes in the context of evolution. The aim of this EMBO workshop is to bring together international scientists with distinct, but complementary expertises on interpreting genome variation, on mechanisms of gene regulation and on in vivo synthetic biology approaches. This allows a comprehensive overview that goes from fundamental principles encoded in genomes to their ultimate biological significance on the formation of living, evolving organisms.

An exciting line-up of speakers (keynote lectures by Edith Heard, Mike Levine and Neil Shubin) will cover the following topics:

– Genomics of ecological adaptation
– Evolution of cell types
– Mechanisms of regulatory variation
– 3D genome organization and structure
– Synthetic biology approaches to model evolution

There will be short talks selected from abstracts, as well as ample time for networking.

Fee waiver, travel and childcare grants available.

Registration and more information: https://meetings.embo.org/event/23-animal-genomes

Hope to see many of you there!!

#EMBOevoAnimalGenomes

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A recent paper in Nature Cell Biology entitled ‘Co-option of epidermal cells enables touch sensing’ reports a new type of specialised epidermal cells involved in touch sensing in Drosophila. We caught up with Dr Federica Mangione, the first author of this paper, to find out more about the story behind the paper.

How did you get started on this project?

I joined the Tapon lab for my postdoc, aiming to study how cell differentiation impacts the structure and function of the somatosensory system, using my beloved Drosophila as an in vivo model. I initially wanted to understand how the tactile bristles, hair follicle-like structures decorating the adult epidermis, develop to allow the adult fruit fly to sense tactile stimuli. Given that the terminal differentiation of these touch-sensitive organs was largely unexplored, what I did first was to visualize this developmental stage, combining bristle-specific genetic labelling with live imaging. While analysing the cellular dynamics underlying the differentiation of the four lineage-related cell types that make up each bristle within the epidermis, I identified the epidermal F-Cell as a novel cell type in the assembly of the mature tactile organ. The temporal and spatial precision underlying the acquisition of the F-Cell fate led us to pursue a detailed study on the structure and function of the tactile bristle and its association with the F-Cell.

What was known about the role of epidermal cells in the function of touch-sensitive organs before your work?

The epidermis is the outermost layer of animals’ body, and it integrates various specialized cells and cellular structures that associate with sensory neurons to shape the sense of touch. In mammals, specialized cells of epidermal origin include the Merkel cells and a subset of the cells making up the hair follicles. While both Merkel cells and hair follicles associate with specific subsets of sensory neurons for touch sensing, the specific role of the epidermal cells of the hair follicles in touch sensation is not well understood. Our work shows that the tactile bristles, hair follicle-like structure in the Drosophila epidermis, associate with specialized epidermal cells, the F-Cell, to sense touch and reveal that the insect epidermis also contains specialized epidermal cells involved in sensory detection.  

Can you summarise your key findings?

One key finding is that F-Cell fate specification occurs post-mitotically: selective elimination of the F-Cell through laser microsurgery induced de novo specification of the F-Cell fate in the remaining epidermal cell adjoining each tactile bristle. The precise dynamic of this event led us to perform a series of genetic and optical experiments which, together, indicated that the shaft cell of the bristle is orchestrating a short-range signalling to select F-Cell fate within the epidermis. Another key finding is that this short-range signalling is dependent on the conserved epidermal growth factor receptor (EGFR) signalling. While corroborating these findings, we asked what happens after F-Cell fate acquisition. Through temporal volume electron microscopy (vEM) and light microscopy during the terminal differentiation of the epidermis, we established that the F-Cell is the only epidermal cell that changes shape to wrap around the tactile bristle. The close association between the F-Cell and the tactile bristle suggested a functional requirement for this cell in touch sensing. Through in vivo electrophysiological recordings and behavioural assays, we found that the F-Cell is indeed essential for touch sensing. Altogether, our work established that the F-Cell is a specialized epidermal cell which shapes the functional assembly of the tactile bristles.

This interdisciplinary work involved diverse expertise, can you talk a bit about your experience collaborating with people in other fields?

Collaborating with people with different known-how and points of view has been incredibly beneficial, both professionally and personally. By working closely with Catherine Maclachlan in the team of Lucy Collinson (The Francis Crick Institute, London, UK), I have learned the many steps behind the beauty of an EM image and the power of vEM in gaining information on cellular morphologies in 3D. I am looking forward to discovering more about the cells of the tactile bristles through EM as I carry on working together with this great team of experts! Working with Joshua Titlow in the team of Ilan Davis (University of Oxford, UK) has been a fantastic experience too! He guided me through the complex process of generating a successful recording of neuronal activity and I am so grateful for his dedication and patience during my many visits to Oxford. This collaboration definitely stoked my passion for neuroscience, which will stay with me for the rest of my career. I feel fortunate to have met Michel Gho (Sorbonne University, Paris, FR) while I was characterizing the genetic basis of F-Cell fate specification. Collaborating with a leading expert in bristle development and genetics such as him has been an absolute honour and of great help to focus on EGFR as a key signal for F-Cell fate specification. All the support from our collaborators have been crucial to shape this paper the way it is!

Did you have any eureka moment that has stuck with you?

One in particular, indeed! While performing live imaging, I observed that, at some point during their differentiation, the cells expressing a bristle-specific cell marker changed from four to five. I could not detect any cell division within the bristle lineage or outside in the epidermis at that time, so how did this switch from four to five occurs? And why? This observation had me puzzled for a while! Three decades of studies established that each bristle is composed of four cell types, all derived from a single precursor cell, so why was I counting 5 instead? How is it that 2+2=5? The eureka moment arrived within the first 2 years of studies, when I found that specific manipulations of bristle cells were affecting the appearance of the F(ifth)-Cell. This told me that the F-Cell is co-opted by the tactile bristle form the neighbouring epidermis, and this makes the impossible possible: 2+2 really equals 5! The 2 pairs of sister cells in the bristle progenitor lineage require “a fifth element” for the assembly of a functional tactile organ. Eureka!

And the flipside: were there any moments of frustration or despair?

Finding a new cell type is very exciting! A flipside, however, is that gaining insights into what makes an uncharacterized cell type unique is quite challenging experimentally. For example, after first observing the F-Cell, I didn’t have any genetic tools to manipulate gene expression in a restricted manner for quite a long time. Also, many of the genetic manipulations I was initially testing affected the fate of bristle cells too, preventing me from cleanly disentangling bristle and F-Cell specification. These obstacles were successfully overcome by combining laser microsurgery with live imaging to target individual cells and in a temporally controlled manner (PMID: 36685184). Performing light and electron microscopy imaging was also technically challenging, especially at later stages of development, when the epidermis become stiffer to form the adult exoskeleton of the fruit fly. We dedicated a lot of effort in optimizing sample preparations and imaging set ups, which definitely worthwhile as we were able to gain access to these developmental stages too! The limited/intermittent access to the lab during the pandemic was also very frustrating of course. Support from the lab helped me in keeping a positive attitude and I saved ‘positive energy stores’ for optimizing experimental designs and close gaps in the project once I was back in the lab.

Why do you think the role of the F-Cell was not characterized before?

I have been asked this question many times, and yet I am not sure that there is a ‘right’ answer. The beauty of Drosophila bristles has attracted scientistic for three decades, as they are a powerful cellular context to address fundamental questions about cell fate determination and asymmetric cell divisions. Surprisingly, however, their differentiation dynamics (how the mature tactile organ is built from its constituent cells) was understudied. The reason behind this lack of knowledge remained mysterious to me until I started performing live imaging during bristle differentiation, which revealed various technical challenges. Thus, I would say that the F-Cell remained uncharacterized as accessing to late developmental stages is not straightforward. My love for microscopy and support from the lab and collaborators helped me in overcoming some of these limitations and gaining accessibility to these developmental stages.

What is next for you after this paper?

I discovered the F-Cell shortly after starting my postdoc in the Tapon lab and collecting the data for this paper has been a great journey. This journey is still going on! There are many aspects of the development of this cell and its association with the tactile bristle that I wish to explore further. I am now completing my postdoctoral training and I am very excited about the prospect of leading a research team in the future and gain more insight into the cell biology of touch!

If you are interested in learning more about the volume electron microscopy (vEM) technique used in this paper, check out the FocalPlane post ‘Inputs and Outputs of vEM in a Sensory System‘.

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In October 2020, we started to observe haemorrhages in the human fetal brain tissue that we received from the HDBR. We were previously using the tissue from HDBR to investigate features of typical cortical development, but we quickly realised that we would need to change track and investigate why these tissue samples contained these haemorrhages, and if this was linked to the COVID-19 pandemic we were in the middle of.

Two and a half years after receiving the first haemorrhagic sample arrived in the lab, we published the paper in Brain (https://doi.org/10.1093/brain/awac372). Here, we (first author Marco Massimo and second author Carlotta Barelli) share the story behind the paper. 

How did you get started on this project?  

Marco Massimo: I always say that this project ‘happened’ to us, as it was totally unexpected. In our lab we work with human fetal brain tissue provided by the Human Developmental Biology Resource HDBR (https://www.hdbr.org). It was October 2020 when HDBR sent us the first haemorrhagic sample. Although haemorrhages in fetal cortex have been observed, they are extremely rare, and initially we were all surprised to see such an injured sample. Over the following months we kept receiving more and more samples presenting haemorrhages and it got to the point that we couldn’t do our experiments investigating typical cortex development anymore! As you all will remember, in October 2020, in the UK, we were in the middle of the SARS-CoV-2 pandemic. Covid cases per day were remarkably high and a vaccine was yet to be offered to the public. We had never received this kind of injured samples before the pandemic, and it is highly unlikely to observe such a high number of haemorrhagic samples in such a short amount of time. That’s why we thought that the highly unusual number of haemorrhagic samples might have something to do with the ongoing Covid19 pandemic. So, this is how we began this project, we hypothesised that those haemorrhages could be associated with SARS-CoV-2, and, with the support of HDBR, together with our collaborators in Trieste and Edinburgh, we started investigating this option. 

Carlotta Barelli: I had already been working in the lab for a couple of months as an undergraduate internship student when we started receiving an abnormally high number of human fetal brain tissue samples displaying cortical haemorrhages. These samples could not be used to study normal brain development and in December 2020 we had received enough of these haemorrhagic samples to start analysing them. Due to the timing, we began investigating whether SARS-CoV-2 could be involved in the injuries observed in these fetal brain tissue samples.

Can you summarise your findings? 

MM and CB:  In our study we report SARS-CoV-2 infection in human fetal brain in association with haemorrhage, disrupted endothelial integrity and infiltration of immune cells in the developing cortex. 

Cortical haemorrhages were linked to a reduction in blood vessel integrity and an increase in immune cell infiltration into the foetal brain. Our findings indicate that SARS-CoV-2 infection may affect the foetal brain during early gestation and highlight the need for further study of its impact on subsequent neurological development. 

Video abstract below:

When doing the research, did you have any surprising results? 

MM: The whole project was a surprise. I guess the biggest shock was when we first detected the SARS-CoV-2 spike protein in the choroid plexus and in the cortex of haemorrhagic samples. That was the proof that there was an association between SARS-CoV-2 infection and the haemorrhages that we had observed. 

CB: It was interesting to see that the majority of the haemorrhagic samples were between 12-14 post conception weeks (pcw). The haemorrhages found in these younger samples (12-14 pcw) were more recent than the haemorrhages found in older samples (19-21 pcw). This suggests a critical window of development where viral infection could have more serious consequences on fetal brain health. Specifically, the integrity of the vasculature could be more severely affected at these younger stages (12-14 pcw) when the blood-brain barrier is still forming, making the brain more susceptible to neurovascular damage.

What were the challenges you faced when working on this project? 

MM: To me the biggest challenge was keeping all the data organised. We processed 26 different samples (plus a similar number of aged-matched controls) which came with a unique 5-digit HDBR number that we had to replace with other codes in order to make our analysis blind. Hundreds of immunofluorescence stainings, for tens of biological markers, had to be imaged generating a huge amount of data that had to be properly saved, analysed and ultimately had to be linked back to all the samples examined. 

Another challenge, given the nature of this research, was that before sharing our results we had to be completely sure that our data was correct. We had to be extra careful in analysing and evaluating our staining, using isotype control antibodies, and making sure our results were consistent with our collaborators’.

CB: Due to the limited knowledge on such a new topic, it was hard to investigate the link between SARS-CoV-2 infection and the high incidence of cortical haemorrhages. When we got started on the project, the only studies on the impact of SARS-CoV-2 infection on the brain had been carried out in cortical organoids, which lack vasculature as well as immune cells. We asked various labs with expertise in brain development and maternal infection, but nobody had ever seen such injuries in human fetal brain tissue samples. This was how we started collaborating with the Giacca, Miron and Williams labs whose contribution was key to progress in this project. 

What impact will/should your results have on public health advice? 

MM: This is an important finding, given that the Covid19 pandemic is still ongoing, and it could have an impact on public health advice. At the time it wasn’t clear if SARS-CoV-2 could be passed from mother to foetus and what the consequences of SARS-CoV-2 infection on foetal brain could be. Although, we still don’t know if these haemorrhages are the indirect result of an immune reaction from the mother or are a direct effect of the viral infection, we thought it was important to share our findings with both the scientific community and the general public, so that everyone was aware.

KL (Katie Long): As the mechanisms leading to the haemorrhages are not yet understood, we aren’t currently in a position to give public health advice, however our colleague Professor Lucilla Poston CBE, Professor of Maternal & Fetal Health at King’s College London, recommended “We know that severe viral infection may influence the fetal brain, but this important study is the first to suggest that this may occur in pregnancies affected by COVID infection. Whatever the cause, a direct effect of the virus or an indirect consequence of maternal infection, this study highlights the need for pregnant women to be vaccinated against COVID-19, thus avoiding complications for both mother and baby.”

CB: Our results should raise awareness on maternal viral infection during pregnancy and encourage pregnant women to take vaccination against SARS-CoV-2. Our study also highlights the need to better understand the risks associated with maternal SARS-CoV-2 infection and its impact on later neurological development.

Where will this story take the lab, and more broadly research in this area? 

KL: We are still receiving fetal brain samples with haemorrhages, although the incidence of this has slowed significantly after pregnant women were offered the COVID-19 vaccines. We will continue to try to understand why these haemorrhages occur and what impact they might have on the developing brain. 

What next for you after this paper?  

 MM: This was my very first paper and I am glad to have contributed to this important finding. I learnt a lot from this, and I am proud of the work we all did. As a 2^nd year PhD student my main focus now is to investigate neuronal migration disorders in the human fetal brain which is what my project was originally about. Even though I won’t have time to continue this research, as I have to prioritise my PhD project, I will be happy to help and support whoever will keep working on this. 

CB: I have now left the lab and started a PhD focusing on glioblastoma and neural stem cells. Despite the shift in research topics, working on this project has taught me a lot about academic research. Specifically, it showed me how scientific research is often nonlinear, results are sometimes unexpected, publishing can be quite complex but, ultimately, the whole process is extremely rewarding.

(1 votes)

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The fifth episode of Made the Same Way, a podcast produced by the Wellcome-funded Human Developmental Biology Initiative, features Lucía Cabriales Torrijos discussing human lung development with performer Beth (aka BABYFLXKCO).

At the end of the episode, the pair collaborate on an original piece of music inspired by their conversation.

It’s amazing how there are options if someone is born premature.

-Beth

About the participants

Lucía is a biophysicist who loves to understand how the cells that make up our bodies perceive and respond to mechanical forces. For the last couple of years, her research has focussed on mimicking foetal breathing movements to understand how these affect cell functions (differentiation) in the formation of the lung. Apart from science, Lucía is interested in art and loves going to museums, the theatre and the cinema.

Beth, aka Babyflxcko, is a 23 year old female singer, songwriter and producer creating soulful jazz, R&B instrumentals and soulful melodies. Brought up in a musical family, she always had a passion for music, writing her first song at just 12 years old. But it wasn’t until she hit 19, living alone in London that she decided to pursue and create her own music full-time.

She released her first EP, Emotions, in 2021 after working alongside other musicians developing musical skills on a project with Reform Radio called Soundcamp 2021. Her musical influences include Jhene Aiko, Billie Eilish and Amy Whinehouse, just to name a few. She is known for doing shows in Manchester, Sheffield and local areas.

Beth has also recently released a new single, Inhalando Y Exhalando (the original music that she created as part of this podcast) on all streaming platforms. You can listen and download here.

Please subscribe and listen to Made the Same Way on Apple podcasts, Spotify, or wherever you get your podcasts. If you enjoy the podcast, please rate and review us on Apple podcasts to help others find us!

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Calling all developmental biology postdocs and graduate students!

Interested in attending an exciting meeting? Want to expand your dev bio network? Want to present your work to a supportive audience? 

Come to the 2023 Developmental Biology Gordon Research Conference and Seminar

Date: June 25 – 30

Venue: Mount Holyoke College, Mass, USA

Abstract deadline May 21, 2023

The organisers have raised significant funds to support registration fees and travel grants for postdocs and graduate students. If you need financial assistance please contact the organisers.

More details visit:
Gordon Research Conference: https://www.grc.org/developmental-biology-conference/2023/
Gordon Research Seminar: https://www.grc.org/developmental-biology-grs-conference/2023/

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“You can boil them, freeze them, throw them into outer space – and they will survive. So how can we use these incredible adaptations to solve some of our own problems?”

Dr Sally Le Plage

In the latest episode of the Genetics Unzipped podcast, we’re going microscopic, exploring what tiny tardigrades can teach us about DNA damage, vaccine distribution and even astronaut health in space.

Genetics Unzipped is the podcast from The Genetics Society. Full transcript, links and references available online at GeneticsUnzipped.com.

Subscribe from Apple podcasts, Spotify, or wherever you get your podcasts.

Head over to GeneticsUnzipped.com to catch up on our extensive back catalogue.If you enjoy the show, please do rate and review on Apple podcasts and help to spread the word on social media. And you can always send feedback and suggestions for future episodes and guests to podcast@geneticsunzipped.com Follow us on Twitter – @geneticsunzip

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Dr. Natalia (Natasha) Shylo, Dr. Paul Trainor and colleagues at Stowers Institute for Medical Research in Kansas City, Missouri, USA recently published an article in Frontiers in Cell and Developmental Biology, titled “Morphological changes and two Nodal paralogs drive left-right asymmetry in the squamate veiled chameleon (C. Calyptratus).” Here is a behind the scenes look into using veiled chameleons as a research organism.

How did you get started on this project?

This project began like a lot of very cool studies do, completely accidentally. We were wrapping up a project describing neural crest cell patterning in veiled chameleons started by a former PhD student Dr. Raul Diaz, and Dr. Natasha Shylo created a staging series of veiled chameleon embryo development to go with the study (Diaz et al., 2019). Based on her prior work in left-right patterning, Dr. Shylo then recognized the potential of veiled chameleons to understand how left-right patterning occurs in non-avian reptiles. When we started this work in 2019, nothing was known about left-right patterning in non-avian reptiles. And it was going to be easy (famous last words), since we already had some of the key reagents – Shh and Fgf8 RNA in situ probes from our previous work in chameleon limb patterning (Diaz and Trainor, 2015), and a Nodal probe for a gastrulation study (Stower et al., 2015). Shh was the first molecular marker ever published with asymmetric molecular expression in chicken, so it was a logical starting point. Also given the presence of cilia and their known roles in left-right organizer function, we also searched for cilia using SEM. But Shh was not asymmetrically expressed in veiled chameleon embryos, and we found nothing that resembled motile cilia in the blastopore region of the embryo.

What was known about left-right patterning in non-avian reptiles before your work?

Left-right patterning in non-avian reptiles was a black box when we started this project. However, we were not the only ones curious to tackle this question. As we were trying to figure out the steps of the Nodal signaling cascade and what happens in an organism that doesn’t use cilia in its left-right organizer, Dr. Hiroshi Hamada’s group published a paper revealing that turtles and geckos also do not use motile cilia to establish left-right patterning (Kajikawa et al., 2020). We were able to build on those observations and realized we were looking at the “wrong” Nodal gene. Nodal1, as we now refer to it, was not supposed to exist in chameleons. It is the only Nodal paralog present in mammalian genomes, but has been lost from the genomes of chickens, geckos, and turtles, which retained Nodal2 instead. It turned out that the veiled chameleon genome contains two Nodal genes – both retained from a duplication event in jawed vertebrates.

What made you choose the veiled chameleon as your model organism?

Although we have a good understanding of early developmental events in many vertebrate model organisms, few studies if any involved the reptile clade. This is because at the time lizards and snakes lay their eggs, their embryos are already at limb bud stages of development, which is far too late to study left-right patterning, gastrulation and neurulation. We became interested in veiled chameleons because their embryos are pre-gastrula stage at the time of oviposition and because of their sexually dimorphic casque, which we hypothesized was neural crest cell derived. Fortunately, veiled chameleons are a popular pet with established husbandry. They breed year-round and lay large clutches of eggs. Dr. Shylo came to the lab with expertise in left-right patterning, and veiled chameleons proved to be a perfect research organism to study the mechanisms establishing left-right asymmetry in non-avian reptiles.

How is it like working with veiled chameleons?

One must be patient when working with veiled chameleons because their development is really slow. It can take up to 70 days to accomplish gastrulation, and a week to establish left-right patterning, compared to about 6 hours in mice, which means veiled chameleons allow for a much finer temporal resolution of key developmental processes. We stagger chameleon mating, and consequently always have an abundance of embryos at various stages of development throughout the year. Veiled chameleon eggs are soft shelled, which means we can’t manipulate the embryos in ovo like chicken embryos, but they are amendable to ex ovo culture, lineage tracing, time lapse imaging and most molecular techniques. 

Can you summarise your key findings?

We used veiled chameleons to study the evolution of developmental mechanisms and obtain a deeper understanding of how left-right patterning is established in non-avian reptiles. We found that like chickens, veiled chameleons do not use motile cilia in their left-right organizer to establish left-right asymmetry. Instead, through live imaging, we observed asymmetric morphological changes in the embryo, which precede, and likely initiate molecular asymmetry. We further discovered that veiled chameleons have retained two Nodal genes – Nodal1 and Nodal2 – from a duplication event in jawed vertebrates. In comparison, mammals have only Nodal1, whereas avians have retained Nodal2. This work has laid the foundation for our future studies, aimed at understanding in greater detail the mechanisms and processes that establish left-right asymmetry in diverse groups of amniotes.

Were you surprised to find that the veiled chameleons do not have motile cilia in their left-right organizer?

Not entirely. Going into this project, the outcome was always going to be binary – they will have motile cilia or not. It has been known for a long time that avian embryos do not have motile cilia in their left-right organizer, so it was reasonable to expect that all reptiles might be the same. What was surprising was the pattern of Shh expression, because Shh is expressed asymmetrically around the node in chickens and pigs (pigs also lack motile cilia in their left-right organizer). In veiled chameleon embryos, Shh is expressed symmetrically in the floor plate, but major morphological changes in the embryo push the Shh expressing tissues to the left. In another surprise and again distinct from chickens and pigs, veiled chameleons don’t use a primitive streak for gastrulation, and appear to lack a morphological node structure. We presume that the blastopore slit in chameleons carries out the function of the left-right organizer, but this remains to be determined.

Did you have any particular result or eureka moment that has stuck with you?

We knew that imaging development live would be key to our understanding of left-right patterning in chameleons, and we collected multiple movies at various stages of development, but no matter how we squinted, tilted our heads, or what type of analysis we used, we could not find consistent robust asymmetric cellular movements in the embryos we imaged. However, in a fortuitous meeting with collaborator and co-author Dr. Sarah E. Smith, viewing the movies in the transverse optical plane revealed an unmistakable asymmetric tilt that occurred reproducibly in all of our movies, which pushes the Shh expression tissue to the left at the same precise stage of development! We still think that the gross morphological rearrangement that we reported is driven by finer cellular movements, and we will continue our work with chameleons to figure out where, when, and how it all starts.

And the flipside: were there any moments of frustration or despair?

As mentioned earlier, Shh was the first molecular marker that we characterized, and it appeared perfectly symmetrical at every stage that we initially examined. This observation was consistent with a report in turtles and geckos from Dr. Hiroshi Hamada’s lab. Apparently, we had a model system in which the left-right organizer lacked motile cilia, and Shh was symmetrically expressed, and this contradicted everything we knew from mice (motile cilia) and chickens (asymmetric Shh). However, it made some sense, since chameleons don’t have a conventional node that rotates. As we started to prepare the manuscript, Dr. Shylo realized a broader time course of Shh expression was required, and there it was, unmistakable asymmetrically displaced Shh expressing tissue! Only these developmental stages were much earlier than when asymmetric Nodal expression is observed! Thus, an initial moment of frustration turned into weeks of excitement. We had simply been looking too late in development. These data revealed that morphological changes occur in a veiled chameleon embryo well before we can detect asymmetric Nodal expression, opening up new models and mechanisms to explore.

Natasha – What brought to you join Paul’s lab? And what is next for you after this paper?

My Ph.D. focused on the ciliary gene Tmem107 in a mouse mutant which exhibited left-right patterning defects (Shylo et al., 2020). Work with a collaborator revealed that these mice also had a neural crest defect, which made me curious about roles for cilia in neural crest cell specification and migration (Cela et al., 2018). So I came to Paul’s lab with a plan to study neural crest cells in mice, but I will continue to study the evolution of developmental mechanisms, particularly with respect to left-right patterning and gastrulation.

I plan to seek out a faculty position in the next year or two, and establish a laboratory to study gastrulation, left-right patterning, and other early developmental processes, using veiled chameleons as a model for early amniotic development. Although my focus has changed dramatically through a series of serendipitous events, there is no other place I could have done this work as efficiently as in Paul’s lab at Stowers Institute. To my knowledge, we maintain the largest colony of veiled chameleons used specifically for research. We have recently sequenced the veiled chameleon genome and once the annotation is finalized, we will have all the genetic, molecular and cellular tools we need to functionally study the evolution of developmental mechanisms with an emphasis on early development in these reptiles. My message to other postdocs based on my experience is to be brave, and if an amazing project summons your attention, it is OK to completely switch directions and your scientific focus. Go for it.

Paul – Where will this story take the lab?

Veiled chameleons exhibit a number of interesting morphological features including a cranial casque, forelimb and hindlimb clefting, and wrists and ankles that function like balls and sockets instead of hinges. Chameleons also have a projectile tongue, a prehensile tail, and they can color change. All of these features make chameleons very well suited for arboreal environments. With annotation of our newly sequenced genome nearly complete, we will soon be able to tackle functional genetic questions in ecological-evolutionary-developmental biology using veiled chameleons in concert with traditional model organisms.

References

CELA, P., HAMPL, M., SHYLO, N. A., CHRISTOPHER, K. J., KAVKOVA, M., LANDOVA, M., ZIKMUND, T., WEATHERBEE, S. D., KAISER, J. & BUCHTOVA, M. 2018. Ciliopathy Protein Tmem107 Plays Multiple Roles in Craniofacial Development. J Dent Res, 97, 108-117.

DIAZ, R. E., JR., SHYLO, N. A., ROELLIG, D., BRONNER, M. & TRAINOR, P. A. 2019. Filling in the phylogenetic gaps: Induction, migration, and differentiation of neural crest cells in a squamate reptile, the veiled chameleon (Chamaeleo calyptratus). Dev Dyn, 248, 709-727.

DIAZ, R. E., JR. & TRAINOR, P. A. 2015. Hand/foot splitting and the ‘re-evolution’ of mesopodial skeletal elements during the evolution and radiation of chameleons. BMC Evol Biol, 15, 184.

KAJIKAWA, E., HORO, U., IDE, T., MIZUNO, K., MINEGISHI, K., HARA, Y., IKAWA, Y., NISHIMURA, H., UCHIKAWA, M., KIYONARI, H., KURAKU, S. & HAMADA, H. 2020. Nodal paralogues underlie distinct mechanisms for visceral left-right asymmetry in reptiles and mammals. Nat Ecol Evol, 4, 261-269.

SHYLO, N. A., EMMANOUIL, E., RAMRATTAN, D. & WEATHERBEE, S. D. 2020. Loss of ciliary transition zone protein TMEM107 leads to heterotaxy in mice. Dev Biol, 460, 187-199.

SHYLO, N. A., SMITH, S. E., PRICE, A. J., GUO, F., MCCLAIN, M. & TRAINOR, P. A. 2023. Morphological changes and two Nodal paralogs drive left-right asymmetry in the squamate veiled chameleon (C. calyptratus). Frontiers in Cell and Developmental Biology, 11.

STOWER, M. J., DIAZ, R. E., FERNANDEZ, L. C., CROTHER, M. W., CROTHER, B., MARCO, A., TRAINOR, P. A., SRINIVAS, S. & BERTOCCHINI, F. 2015. Bi-modal strategy of gastrulation in reptiles. Dev Dyn, 244, 1144-1157.

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The fourth episode of the Wellcome-funded Human Developmental Biology Initiative‘s new podcast, Made the Same Way, features scientist Emily Calderbank and rapper Olivia (aka FREEQUENCY3) discussing human embryonic haematopoiesis.

At the end of the episode, the pair collaborate on an original piece of music which reflects their conversation.

Right now, every second, your blood is making 3 million cells!

Emily Calderbank

About the participants

Emily Calderbank is a postdoctoral researcher at the Stem Cell Institute, part of the University of Cambridge. Her research focuses on the production and maintenance of human blood throughout life, from embryo to adult, and the role that inflammatory signals may play in this process.

In her spare time, she enjoys listening to podcasts and baking.

Olivia, AKA FREEQUENCY3 is an Alternative HipHop rapper, DJ and host. FREEQUENCY3 explores emotion, values & the ripples of life through music, both written and freestyle. Over the past year FREEQUENCY3 has supported Dizraeli on his UK Tour and rapped in the ‘CalibySnoop’ Cypher, which brought together some of Manchester’s best rappers to launch Snoop Dogg’s CalibySnoop wine in the UK.

In her spare time, she enjoys being around friends and family, listening to music, watching tv and relaxing.

Please subscribe and listen to Made the Same Way on Apple podcasts, Spotify, or wherever you get your podcasts. If you enjoy the podcast, please rate and review us on Apple podcasts to help others find us!

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One of the crowd-favourite giveaways here at the Node is our collection of postcards. With our supplies dwindling, we are planning to reprint some of the postcards, and take this opportunity to add some more #devbio favourites to our collection.

Thank you to all the researchers who have submitted their images to the Node postcard competition back in April. We have now narrowed down to the final 8, and would like to see which ones the community like to feature on our postcards. The top 4 will be printed on our postcards, and the winner will be also be featured on the cover of a ‘Development’ issue in 2023.

Please vote for your favourite image at the bottom of the page. The voting will close on Sunday 4 June 11:59pm.

“Geographical Maps“

Depicted is a digital section of the developing eye in a zebrafish. Specifically, these are support cells of the eye called glia cells, which have undergone 3D data processing to extract the surface of these cells. Different colours represent different depths in the studied eye. Technique: The image was acquired with the Zeiss LSM 900 AiryScan microscope, using a 40x water-immersion LD C-Apochromat (NA 1.1) objective. Processing was conducted using Fiji. Following image rotation in 3D, data were segmented and the surface extracted. Using depth-coding and application of different colour-palettes achieved the different colorations seen. 

Drosophila larvae

This shows heat-fixed Drosophila larvae expressing an infrared fluorescent protein (IFP) in the tracheal system using the Gal4/UAS system. Images were acquired in a confocal microscope (Nikon A1R+) with a 10x objective and using the mosaic modality. Stitching was done using the microscope’s software (Nikon NIS-Elements). The images were Z-projected and pseudocolored in Fiji and further processed using Inkscape.

Hatching embryo

Immunostaining of a hatching mouse blastocyst imaged with confocal microscopy

Tarsal Claw

This scanning electron microscope (SEM) image of the tarsal claw of the horsefly (Tabanus sulcifrons) juxtaposes the complexity and simplicity of “nature’s Velcro.” The menacing sturdiness of the tarsal claws contrasts with the delicate nature of the tarsal pad, with fine, hooked hairs that allow the fly to hold on to animal fur.

Human dopaminergic neurons

This image shows a culture of human dopaminergic neurons generated from human stem cells acquired via super-resolution Airyscan confocal microscopy at the University of Oxford Micron facility. Dopaminergic neurons are the main cell type that deteriorate in Parkinson’s disease, partly due to toxic build-up of a protein called alpha-synuclein.

Arabidopsis leaf

Cells on the epidermis of a 3 day old Arabidopsis leaf. This is an adaptation of a linocut print created based on a microscopy image.

Catshark embryo

Ventral view maximum intensity projection from an immunofluorescence staining labeling the developing nervous system (primarily nerves and ganglia) of a stage 30 small-spotted catshark embryo (Scyliorhinus canicula). The image was acquired using a ZEISS LSM980 with Airyscan2 confocal microscope, stitched and processed using ZEN software from the same microscope.

Xenopus laevis skeleton

Skeletal staining (alizarin red and alcian blue) of a Xenopus laevis at stage 62. Stage 51 larva was treated with a Cyp26a inhibitor during forelimb regeneration. Notice proximo-distal duplication in the left forelimb.

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