A mutation from a human patient with a rare metabolic disorder has been replicated in the Japanese rice fish. Researchers from the Centre for Organismal Studies Heidelberg, Germany, have developed a fish model to study disorders caused by a deficiency in the process of adding sugar molecules to proteins. These findings, published in the journal Development, provide a system to study the causes of complex metabolic disorders in humans.
In Alg mutant embryos, rod cells are initially born but not maintained and undergo programmed cell death indicated in magenta (TUNEL staining). Credit: Clara Becker.
Human cells are kept healthy by the activity of millions of proteins. These proteins are modified in different ways, such as by adding sugar molecules to them, which can be crucial for them to function properly. Given this importance, defects in the sugar-adding process are often lethal at the very early stages of development. In rare cases, however, patients can develop sugar-adding deficiencies that result in a range of metabolic diseases, known collectively as ‘congenital disorders of glycosylation’ (CDG). These disorders are caused by defects in the enzymes involved in the sugar-adding process. For example, ALG2-CDG (or CDG-Ii) is a disorder caused by mutations in the ALG2 enzyme, which combines sugar molecules together. ALG2-CDG patients appear unaffected at birth, but later develop problems in different organs, such as the eyes, brain and muscles.
The rarity, variety and complexity of these disorders has made them difficult to study, especially in the context of the whole body. Now, scientists have developed the Japanese rice fish (also known as the medaka) as a model system for studying such disorders. “Fish are particularly good models for these disorders because they develop outside the mother, making them very suitable for studying early embryonic defects,” said Professor Joachim Wittbrodt from the Centre for Organismal Studies, who led the study with Dr Thomas Thumberger. “The medaka is particularly well suited to this type of research, because we can edit the genome with high efficiency and we can utilise genetically identical lines.”
The team used CRISPR/Cas9 genome editing to introduce mutations in the medaka’s alg2 gene, in the same region where mutations had been found in a patient with ALG2-CDG. The scientists found that many of the symptoms of the patient, such as neuronal problems, were replicated in the fish. “We basically discovered a large fraction of the symptoms that had been described in the patient. Unlike studies of cells in a dish, the fish model provides the full spectrum of different cell types in an organism, which produced some unexpected results. For example, even though all the cells lack ALG2 enzymatic activity, only some cells respond, while their neighbours do not. In the fish eye, the cone (colour-sensing) cells are unaffected, whereas rod cells (which are required for vision in low light) form initially, but are then eventually lost. This defect, known as retinitis pigmentosa, is a symptom of many patients with congenital disorders of glycosylation,” explained Professor Wittbrodt. “We want to identify the proteins that require ALG2 in rod cells to understand their involvement in maintaining rod-cell function,” he added.
Importantly, these defects could be prevented by supplying fully-functional Alg2 to the fish eggs. Moving forward, the researchers plan to use this animal model to study the effects of human ALG2 mutations further. Professor Wittbrodt said, “the fact that this disorder can be efficiently rescued opens the door for understanding how different mutations in ALG2 affect its function. We especially want to study the cell type-specific responses in the context of a whole organism.”
The Marín-Juez laboratory, at the CHU Sainte-Justine Research Center, is recruiting a PhD student and a postdoctoral fellow (4-year fully funded positions). Our laboratory is interested in the cellular and molecular mechanisms regulating cardiac regeneration. The successful applicant will join the Marín-Juez laboratory at the CHU Sainte-Justine Research Center, where s/he will have access to state-of-the-art facilities and technology platforms including Advanced imaging platform (light-sheet, spinning-disc confocal, multiphoton, STED super-resolution, etc.), genomics (DropSeq, 10x, Illumina Novaseq) and bioinformatics platforms. CHU Sainte-Justine Research Center provides a thriving scientific environment where the successful applicant will have the opportunity to work with multidisciplinary scientific teams and to collaborate with talented clinicians and researchers.
Research project description
For this project, we are particularly interested in understanding how the cardiac endothelium regulates different aspects of cardiac regeneration and how alterations in the coronary network formation impact the ability of coronary vessels to support tissue replenishment. We have recently found early coronary regeneration as a key determinant of heart regeneration (Marín-Juez et al., PNAS 2016), and identified mechanisms regulating coronary network replenishment to form a vascular scaffold that supports cardiomyocyte regeneration (Marín-Juez et al., Dev Cell 2019). We now seek to define how the different components of the cardiac endothelium regulate tissue replenishment and identify the different mechanisms involved in their regulation of CM proliferation and migration.
Required training and profile
Ph.D. student position: Applicants should have training in vascular biology, molecular biology, cell biology, or related fields. Suitable candidates should be enthusiastic about regenerative and vascular biology. Previous research experience with zebrafish and/or heart regeneration is desired.
Postdoctoral position: We are looking for candidates with a Ph.D. in the biological sciences and laboratory experience in tissue repair/regeneration, cellular, molecular biology, or genetics. Previous experience working with zebrafish, imaging and histology are highly valued but not essential.
Both positions: Candidates with experience in confocal/light-sheet imaging and/or genome engineering are strongly encouraged to apply. Preference will be given to applicants with excellent collaborative and communication skills. The Marín-Juez lab and the CHU Sainte-Justine Research Center subscribe to the principle of equal access to opportunities and encourage women, members of visible and ethnic minorities, persons with disabilities and Indigenous people to apply.
Submit your application
Candidates must send the required documents before 07/31/2021 to Rubén Marín Juez at ruben.marin.juez.hsj@ssss.gouv.qc.ca
Please provide: Curriculum vitæ, Cover letter and References (2 or 3).
Royal Society Publishing has recently published a special issue of Interface Focus entitled Interdisciplinary approaches to dynamics in biology organized by Rubén Pérez-Carrasco and Berta Verd, and featuring lots of content relevant to developmental biology.
We are happy to announce the upcoming EMBO workshop “The Evolution of Animal Genomes”.
The event will take place virtually, from 13-17 September 2021 (Registration and abstract deadline: 12th July 2021)
The development of novel tools to analyze and reconstruct entire genomes open exciting possibilities to understand the appearance of phenotypical traits. This workshop will bring together internationally recognized scientists with distinct, but complementary, expertise in interpreting the effects of genomic variability. The combination of such aspects 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 lecture by Mike Levine) will cover the following topics:
– Principles of genomic adaptation – Evolutionary impact of regulatory variation – From linear to spatial – The 3D genome – Transposable elements as drivers of evolution – Evolution at single-cell resolution
There will be short talks selected from abstracts, as well as ample time for networking.
In the latest episode of Genetics Unzipped, we discover how researchers have used genetic engineering to turn genes into lifesaving drugs such as insulin for people with diabetes, and monoclonal antibodies that are used to treat autoimmune conditions, cancer and infectious diseases like COVID-19.
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
preLights, our sister community site here at The Company of Biologists, just published an interview with developmental biologist and zebrafish aficionado Christian Mosimann. It covers his research history, career trajectory, and, as in this quote, his views on preprints in science:
“I only preprint papers that we send out for peer review at a journal and not to stake a claim on something, and I’ve found this to be very helpful for job searches and for grants….I think the more we normalise preprinting our work we are confident in, the more we can show everyone that nobody is going to scoop you the very next morning if you put your research on a preprint server.”
Oligodendrocyte precursor cells prune axons in the mouse neocortex JoAnn Buchanan, Leila Elabbady, Forrest Collman, Nikolas L. Jorstad, Trygve E. Bakken, Carolyn Ott, Jenna Glatzer, Adam A. Bleckert, Agnes L. Bodor, Derrick Brittan, Daniel J. Bumbarger, Gayathri Mahalingam, Sharmishtaa Seshamani, Casey Schneider-Mizell, Marc M. Takeno, Russel Torres, Wenjing Yin, Rebecca D. Hodge, Manuel Castro, Sven Dorkenwald, Dodam Ih, Chris S. Jordan, Nico Kemnitz, Kisuk Lee, Ran Lu, Thomas Macrina, Shang Mu, Sergiy Popovych, William M. Silversmith, Ignacio Tartavull, Nicholas L. Turner, Alyssa M. Wilson, William Wong, Jingpeng Wu, Aleksandar Zlateski, Jonathan Zung, Jennifer Lippincott-Schwartz, Ed S. Lein, H. Sebastian Seung, Dwight E. Bergles, R. Clay Reid, Nuno Maçarico da Costa
Size-dependent protein segregation creates a spatial switch for Notch signaling and function Minsuk Kwak, Kaden M. Southard, Woon Ryoung Kim, Nam Hyeong Kim, Ramu Gopalappa, Minji An, Hyun Jung Lee, Min K. Kang, Seo Hyun Choi, Justin Farlow, Anastasios Georgakopoulos, Nikolaos K. Robakis, Matthew L. Kutys, Daeha Seo, Hyeong Bum Kim, Yong Ho Kim, Jinwoo Cheon, Zev J. Gartner, Young-wook Jun
Effects of gestational age at birth on perinatal structural brain development in healthy term-born babies Oliver Gale-Grant, Sunniva Fenn-Moltu, Lucas França, Ralica Dimitrova, Daan Christaens, Lucilio Cordero-Grande, Andrew Chew, Shona Falconer, Nicholas Harper, Anthony N Price, Jana Hutter, Emer Hughes, Jonathan O’Muircheartaigh, Mary Rutherford, Serena J Counsell, Daniel Rueckert, Chiara Nosarti, Joseph V Hajnal, Grainne McAlonan, Tomoki Arichi, A David Edwards, Dafnis Batalle
A single short reprogramming early in life improves fitness and increases lifespan in old age Quentin Alle, Enora Le Borgne, Paul Bensadoun, Camille Lemey, Nelly Béchir, Mélissa Gabanou, Fanny Estermann, Christelle Bertrand-Gaday, Laurence Pessemesse, Karine Toupet, Jérôme Vialaret, Christophe Hirtz, Danièle Noël, Christian Jorgensen, François Casas, Ollivier Milhavet, Jean-Marc Lemaitre
Molecular diversity and lineage commitment of human interneuron progenitors Dmitry Velmeshev, Manideep Chavali, Tomasz J. Nowakowski, Mohini Bhade, Simone Mayer, Nitasha Goyal, Beatriz Alvarado, Walter Mancia, Shaohui Wang, Matthew Speir, Maximilian Haeussler, David Rowitch, Arturo Alvarez-Buylla, Eric J. Huang, Mercedes Paredes, Arnold Kriegstein
Novel epigenetic clock for fetal brain development predicts prenatal age for cellular stem cell models and derived neurons Leonard C. Steg, Gemma L. Shireby, Jennifer Imm, Jonathan P. Davies, Alice Franklin, Robert Flynn, Seema C. Namboori, Akshay Bhinge, Aaron R. Jeffries, Joe Burrage, Grant W. A. Neilson, Emma M. Walker, Leo W. Perfect, Jack Price, Grainne McAlonan, Deepak P. Srivastava, Nicholas J. Bray, Emma L. Cope, Kimberly M. Jones, Nicholas D. Allen, Ehsan Pishva, Emma L. Dempster, Katie Lunnon, Jonathan Mill, Eilis Hannon
Longitudinal dynamics of clonal hematopoiesis identifies gene-specific fitness effects Neil A. Robertson, Eric Latorre-Crespo, Maria Terradas-Terradas, Alison C. Purcell, Benjamin J Livesey, Joseph A. Marsh, Lee Murphy, Angie Fawkes, Louise MacGillivray, Mhairi Copland, Riccardo E. Marioni, Sarah E. Harris, Simon R. Cox, Ian J. Deary, Linus J. Schumacher, Kristina Kirschner, Tamir Chandra
In vitro models of the human esophagus reveal ancestrally diverse response to injury Daysha Ferrer-Torres, Joshua H. Wu, Charles J. Zhang, Max A. Hammer, Michael Dame, Angeline Wu, Emily M. Holloway, Kateryna Karpoff, Caroline L. McCarthy, Margaret S Bohm, Sha Huang, Yu-Hwai Tsai, Simon P. Hogan, Danielle Kim Turgeon, Jules Lin, Peter D.R. Higgins, Jonathan Sexton, Jason R. Spence
Microtubule re-organization during female meiosis in C. elegans Ina Lantzsch, Che-Hang Yu, Yu-Zen Chen, Vitaly Zimyanin, Hossein Yazdkhasti, Norbert Lindow, Erik Szentgyörgyi, Ariel Pani, Steffen Prohaska, Martin Srayko, Sebastian Fürthauer, Stefanie Redemann
Scaling of cellular proteome with ploidy Galal Yahya, Paul Menges, Devi Anggraini Ngandiri, Daniel Schulz, Andreas Wallek, Nils Kulak, Matthias Mann, Patrick Cramer, Van Savage, Markus Raeschle, Zuzana Storchova
Minian: An open-source miniscope analysis pipeline Zhe Dong, William Mau, Yu (Susie) Feng, Zachary T. Pennington, Lingxuan Chen, Yosif Zaki, Kanaka Rajan, Tristan Shuman, Daniel Aharoni, Denise J. Cai
“How do we do this at a distance?!” A descriptive study of remote undergraduate research programs during COVID-19 Olivia A. Erickson, Rebecca B. Cole, Jared M. Isaacs, Silvia Alvarez-Clare, Jonathan Arnold, Allison Augustus-Wallace, Joseph C. Ayoob, Alan Berkowitz, Janet Branchaw, Kevin R. Burgio, Charles H. Cannon, Ruben Michael Ceballos, C. Sarah Cohen, Hilary Coller, Jane Disney, Van A. Doze, Margaret J. Eggers, Stacy Farina, Edwin L. Ferguson, Jeffrey J. Gray, Jean T. Greenberg, Alexander Hoffman, Danielle Jensen-Ryan, Robert M. Kao, Alex C. Keene, Johanna E. Kowalko, Steven A. Lopez, Camille Mathis, Mona Minkara, Courtney J. Murren, Mary Jo Ondrechen, Patricia Ordoñez, Anne Osano, Elizabeth Padilla-Crespo, Soubantika Palchoudhury, Hong Qin, Juan Ramírez-Lugo, Jennifer Reithel, Colin A. Shaw, Amber Smith, Rosemary Smith, Adam P. Summers, Fern Tsien, Erin L. Dolan
We are happy to announce that the UK Chick Developmental Biology Meeting 2021 will be held online on Friday 10th September.
This one-day virtual meeting brings together researchers from Universities and Research Institutes across the United Kingdom to promote and further our in-depth strength in using the chick embryo as a model organism to study a variety of topics in developmental biology. The meeting itself is a mix of talks from junior and senior developmental biologists and aims to stimulate productive interactions between research groups and individuals from different subject areas to exchange knowledge and expertise. This meeting will also provide a platform of support for early career researchers to engage with the community during a difficult time.
We are delighted to have Prof Marianne Bronner (Caltech, USA) as our international keynote speaker to join other invited speakers from the UK such as Prof Kate Storey (Dundee), Dr Matt Towers (Sheffield), Dr Siobhan Loughna (Nottingham), Dr Mike McGrew (Roslin) and Dr Fengzhu Xiong (Cambridge).
In addition we will have talks from early career researchers (i.e. those just starting their labs, post docs and graduate students) – so please do let us know if you or someone in your lab has a nice story that they could present please contract and email Dr Gi Fay Mok (g.mok@uea.ac.uk) or Dr Eirini Maniou (e.maniou@ucl.ac.uk) to discuss and submit a short abstract. The deadline for abstract enquiries and submissions is Friday 15th July.
In this episode of the Genetics Unzipped podcast we’re taking to the night skies with a closer look at the genetics of bats. Usually the stuff of horror films and Hallowe’en, these fascinating mammals have many important genetic secrets to share with us about evolution, longevity, immunity and more.
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
This post is to let you know about an initiative to form a European Drosophila Society (EDS), which aims to represent our research community, support common initiatives and infrastructure, as well as oversee the organisation of the biennial European Drosophila Research Conference. We have set up a web site (http://europeandrosophilasociety.org/) where you can register as an EDS member (free!). You can also follow us on Twitter @Fly_EDS. You will find information about Drosophila community news and job postings, as well as the EDRC conferences.
The EDS will be overseen by the European Drosophila Board (EDB), which will reflect the geographic and thematic diversity of our community. To get the EDS under way, we have formed an initial EDB, and plan to hold elections in 2023 to renew EDB membership. Our aim is to be inclusive: we wish to represent and support the whole breadth of European Drosophila research, as well as establish strong ties with other invertebrate/vertebrate/model organism research communities. The EDS exists to promote your research and can only work with your support, therefore we urge to join the EDS by visiting the web site and signing up. You can also contact board members to propose initiatives or offer help to our working groups.
All registered members of the community can post news, events and jobs on the web site, as well as search for Drosophila researchers based on expertise or research interests using our search engine. Group leaders can add their lab to the interactive map of European Drosophila labs. We welcome suggestions of other services we could offer to the Drosophila community.
Sincerely yours,
The European Drosophila Board Michael Boutros, Nick Brown, Virginie Courtier, Eileen Furlong, Alex Gould, Ilona Grunwald Kadow, Gabor Juhasz, Estee Kurant, Bruno Lemaitre, Marco Milan, Lisa Meadows, Ruth Palmer, Frank Schnorrer, Nic Tapon, Luis Teixeira
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