By decoding the genetic mechanisms that control the neurons of the visual system, researchers at UNIGE are unveiling the first steps in the construction of vision, paving the way for regenerative eye medicine. A Press Release from the University of Geneva.
How is the retina formed? And how do neurons differentiate to become individual components of the visual system? By focusing on the early stages of this complex process, researchers at the University of Geneva (UNIGE), Switzerland, in collaboration with the École Polytechnique Fédérale de Lausanne (EPFL), have identified the genetic programmes governing the birth of different types of retinal cells and their capacity to wire to the correct part of the brain, where they transmit visual information. In addition, the discovery of several genes regulating nerve growth allows for the possibility of a boost to optic nerve regeneration in the event of neurodegenerative disease. These results can be discovered in the journal Development.
The visual system of mammals is composed of different types of neurons, each of which must find its place in the brain to enable it to transform stimuli received by the eye into images. There are photoreceptors, which detect light, optic nerve neurons, which send information to the brain, cortical neurons, which form images, or interneurons, which make connections between other cells. Though not yet differentiated in the early stages of embryonic development, these neurons are all produced by progenitor cells that, are capable of giving rise to different categories of specialized neurons. To better understand the exact course of this mechanism and identify the genes at work during retinal construction, researchers studied the dynamics of gene expression in individual cells. “To monitor gene activity in cells and understand the early specification of retinal neurons, we sequenced more than 6,000 cells during retinal development and conducted large-scale bioinformatic analyses,” explains Quentin Lo Giudice, PhD student in the Department of Basic Neurosciences at the UNIGE Faculty of Medicine and first author of this article.
Photoreceptors cells responsible for colour vision. By sequencing one cell at a time, the researchers identified a gene (Rbp4) present in a small number of cells (in green). In purple, photoreceptors in which the Rbp4 gene is not activated.
Mapping a system under construction
In collaboration with Gioele La Manno and Marion Leleu of EPFL, the researchers studied progenitor’s behaviour during the cell cycle as well as during their progressive differentiation. The scientists then mapped very accurately the different cell types of the developing retina and the genetic changes that occur during the early stages of this process. “Beyond their “age”—that is, when they were generated during their embryonic life—the diversity of neurons stems from their position in the retina, which predestines them for a specific target in the brain,” explains Pierre Fabre, senior researcher in the Department of Basic Neurosciences at the UNIGE Faculty of Medicine, who directed this work. “In addition, by predicting the sequential activation of neural genes, we were able to reconstruct several differentiation programs, similar to lineage trees, showing us how the progenitors progress to one cell type or another after their last division.”
The researchers also conducted a second analysis. If the right eye mainly connects essentially to the left side of the brain, and vice versa, a small fraction of neurons in the right eye make connections in the right side of the brain. Indeed, all species with two eyes with overlapping visual fields, such as mammals, must be able to mix information from both eyes in the same part of the brain. This convergence makes it possible to see binocularly and perceive depths or distances. “Knowing this phenomenon, we have genetically and individually “tagged” the cells in order to follow each of them as they progress to their final place in the visual system,” says Quentin Lo Giudice. By comparing the genetic diversity of these two neural populations, researchers discovered 24 genes that could play a key role in three-dimensional vision. “The identification of these gene expression patterns may represent a new molecular code orchestrating retinal wiring to the brain,” adds Dr. Fabre.
Towards regenerative medicine
Even before the neurons reach the brain, they must leave the retina through the optic nerve. The last part of this study identified the molecules that guide neurons on the right path. Moreover, these same molecules also allow the initial growth of axons, the part of neurons that transmits electrical signals to the synapses and thus ensures the passage of information from one neuron to another, as well as about twenty genes that control this process. This discovery is a fundamental step forward for regenerative medicine.
The more we know about the molecules needed to appropriately guide axons, the more likely we are to develop a therapy to treat nerves trauma. “If the optic nerve is cut or damaged, for example by glaucoma, we could imagine reactivating those genes that are usually only active during the embryonic development phase. By stimulating axon growth, we could allow neurons to stay connected and survive,” explains Dr. Fabre, who plans to launch a research project on this theme. Although the regeneration capacities of neurons are very low, they do exist and techniques to encourage their development must be found. Genetic stimulation of the damaged spinal cord after an accident is based on the same idea and is beginning to show its first successes.
The Kodjabachian lab at the Institute of Developmental Biology of Marseille (IBDM) is seeking a talented postdoctoral scientist with strong background in Cell and/or Developmental Biology, and a keen interest in integrative quantitative biology and interdisciplinary research. Our lab uses advanced imaging techniques (such as confocal videomicroscopy, super-resolution microscopy and 3D electron microscopy) to study the biology of ciliated epithelia at multiple scales.
In vertebrate ciliated epithelia, flows of biological fluids are powered by the coordinated beating of myriads of cilia harbored by multiciliated cells (MCC). This highly choreographed phenomenon raises many biological as well as physical questions among which, MCC spatial organization and at a lower scale centriole multiplication and orientation, as cilia stand upon modified centrioles called basal bodies. The selected candidate will join efforts to decipher the molecular mechanisms underlying these processes, using Xenopus epidermis, inducible MCC culture, and mouse post-natal brain as models.
IBDM offers a vibrant, international, and interactive environment to study the fundamental principles of cell and developmental biology. Furthermore, collaboration with theoreticians, physicists and numerical simulators are being developed on campus, from which our team has started to benefit.
The ideal candidate must hold a PhD for less than two years, and have skills in cell culture, cell imaging, molecular biology, and biochemistry. The position is opened for 3 years starting in December 2019. Applicants must email a CV, a statement of interest and contact details for 2-3 references to laurent.kodjabachian@univ-amu.fr. Applications will be reviewed as received, so motivated applicants are encouraged to apply as soon as possible.
Relevant publications:
Boutin and Kodjabachian. 2019. Current Opinion in Genetics and Development
Our research investigates the fundamental question of how cardiac cells sense and respond to their environment. We seek to understand the mechanisms underlying the regulation of morphogenetic and identity transformations that occur during development and disease. We use the assembly of the heart tube in zebrafish as our model with which to elucidate these mechanisms. Some of the specific research questions we are interested in include: How do multiple tissues interact to regulate large movements and biomechanical force? How do dynamic changes in the extracellular matrix regulate cardiac morphogenesis? How is lumen formation intrinsically and extrinsically encoded? and How is the plasticity of cardiovascular identity regulated? To answer these questions, we take an interdisciplinary approach, combining the genetic and live-imaging strengths of zebrafish with both biomechanics and systems-level methodologies.
If you are interested in joining our lab as a PhD student, please contact us directly at josh@olemiss.edu.
-Additional positions, including a rotation program, are also available in our interdisciplinary graduate program in the department of Biology at the University of Mississippi. For more information about our graduate program including rotations please see biology.olemiss.edu
We seek a biocurator to join the FlyBase group at the University of Cambridge, UK. If you are looking for a fulfilling, fly-related career away from the lab, and enjoy the challenge of organizing complex data clearly and concisely, then this is the job for you!
FlyBase curators extract biological information from scientific articles about the model organism Drosophila melanogaster, recording and organizing these data in template forms and graphical interfaces. Phenotype curators focus on data that illuminate the function of genes based on their mutant phenotypes and genetic interactions. All curated data are subsequently integrated into our central database and made freely available via the FlyBase website.
Additional responsibilities of phenotype curators include: developing strategies/tools to improve curation; enhancing data display/querying on the website; and interacting with the research community through HelpMail and presentations/help desks at research conferences. Curators also contribute to FlyBase publications and have the opportunity to develop computational skills (e.g. Unix, scripting, SQL).
I am pleased to announce a new collaborative interest initiative called DevoWormML, based on work being done in the DevoWorm group. DevoWormML will meet on a weekly basis, and explore the application of machine learning and artificial intelligence to problems in developmental biology. These applications can be geared towards the analysis of imaging data, gaining a better understanding of thought experiments, or anything else relevant to the community.
While “ML” stands for machine learning, participation can include various types of intelligent systems approaches. Our goal is to stimulate interest in new techniques, discover new research domains, and establish new collaborations. Guests are welcome to attend, so if you know an interested colleague, feel free to direct them our way.
Meetings will be Wednesdays at 1pm UTC on Google Meet. Discussions will also take place on the #devowormml channel of OpenWorm Slack (request an invitation). We will discuss organizational details at our first meeting on September 4. If you cannot make this time but are still interested in participating, please contact me. Hope to see you there!
Deficiency in the endocytic adaptor protein PHETA1/2 impairs renal and craniofacial development
Kristin M. Ates, Tong Wang, Trevor Moreland, Rajalakshmi Veeranan-Karmegam, Priya Anand, Wolfgang Wenzel, Hyung-Goo Kim, Lynne A. Wolfe, Joshi Stephen, David R. Adams, Thomas Markello, Cynthia J. Tifft, William A. Gahl, Graydon B. Gonsalvez, May Christine Malicdan, Heather Flanagan-Steet, Y. Albert Pan
The enteric nervous system of the human and mouse colon at a single-cell resolution
Eugene Drokhlyansky, Christopher S. Smillie, Nicholas Van Wittenberghe, Maria Ericsson, Gabriel K. Griffin, Danielle Dionne, Michael S. Cuoco, Max N. Goder-Reiser, Tatyana Sharova, Andrew J. Aguirre, Genevieve M. Boland, Daniel Graham, Orit Rozenblatt-Rosen, Ramnik J. Xavier, Aviv Regev
The skin’s germinative layer from Joost, et al.’s preprint
A molecular cell atlas of the human lung from single cell RNA sequencing
Kyle J. Travaglini, Ahmad N. Nabhan, Lolita Penland, Rahul Sinha, Astrid Gillich, Rene V. Sit, Stephen Chang, Stephanie D. Conley, Yasuo Mori, Jun Seita, Gerald J. Berry, Joseph B. Shrager, Ross J. Metzger, Christin S. Kuo, Norma Neff, Irving L. Weissman, Stephen R. Quake, Mark A. Krasnow
Generation of human neural retina transcriptome atlas by single cell RNA sequencing
Samuel W. Lukowski, Camden Y. Lo, Alexei Sharov, Quan H. Nguyen, Lyujie Fang, Sandy S.C. Hung, Ling Zhu, Ting Zhang, Tu Nguyen, Anne Senabouth, Jafar S. Jabbari, Emily Welby, Jane C. Sowden, Hayley S. Waugh, Adrienne Mackey, Graeme Pollock, Trevor D. Lamb, Peng-Yuan Wang, Alex W. Hewitt, Mark Gillies, Joseph E. Powell, Raymond C.B. Wong
DUX4 regulates oocyte to embryo transition in human
Sanna Vuoristo, Christel Hydén-Granskog, Masahito Yoshihara, Lisa Gawriyski, Anastassius Damdimopoulos, Shruti Bhagat, Kosuke Hashimoto, Kaarel Krjutškov, Sini Ezer, Priit Paluoja, Karolina Lundin, Pauliina Paloviita, Gaëlle Recher, Vipin Ranga, Tomi Airenne, Mahlet Tamirat, Eeva-Mari Jouhilahti, Timo Otonkoski, Juha S. Tapanainen, Hideya Kawaji, Yasuhiro Murakawa, Thomas R. Bürglin, Markku Varjosalo, Mark S. Johnson, Timo Tuuri, Shintaro Katayama, Juha Kere
An integrative view of the regulatory and transcriptional landscapes in mouse hematopoiesis
Guanjue Xiang, Cheryl A. Keller, Elisabeth Heuston, Belinda M. Giardine, Lin An, Alexander Q. Wixom, Amber Miller, April Cockburn, Jens Lichtenberg, Berthold Göttgens, Qunhua Li, David Bodine, Shaun Mahony, James Taylor, Gerd A. Blobel, Mitchell J. Weiss, Yong Cheng, Feng Yue, Jim Hughes, Douglas R. Higgs, Yu Zhang, Ross C. Hardison
Modeling and treating GRIN2A developmental and epileptic encephalopathy in mice
Ariadna Amador, Christopher D. Bostick, Heather Olson, Jurrian Peters, Chad R. Camp, Daniel Krizay, Wenjuan Chen, Wei Han, Weiting Tang, Ayla Kanber, Sukhan Kim, Jia Jie Teoh, Sabrina Petri, Hunki Paek, Ana Kim, Cathleen M. Lutz, Mu Yang, Scott J. Myers, Subhrajit Bhattacharya, Hongjie Yuan, David B. Goldstein, Annapurna Poduri, Michael J. Boland, Stephen F. Traynelis, Wayne N. Frankel
Autophagy mediates temporary reprogramming and dedifferentiation in plant somatic cells
Eleazar Rodriguez, Jonathan Chevalier, Jakob Olsen, Jeppe Ansbøl, Vaitsa Kapousidou, Zhangli Zuo, Steingrim Svenning, Christian Loefke, Stefanie Koemeda, Pedro Serrano Drozdowskyj, Jakub Jez, Gerhard Durnberger, Fabian Kuenzl, Michael Schutzbier, Karl Mechtler, Signe Lolle, Yasin Dagdas, Morten Petersen
Integrated Multi-omic Framework of the Plant Response to Jasmonic Acid
Mark Zander, Mathew G. Lewsey, Natalie M. Clark, Lingling Yin, Anna Bartlett, J. Paola Saldierna Guzmán, Elizabeth Hann, Amber E. Langford, Bruce Jow, Aaron Wise, Joseph R. Nery, Huaming Chen, Ziv Bar-Joseph, Justin W. Walley, Roberto Solano, Joseph R. Ecker
The importance of barrier-free use of colors in images and graphs has been highlighted in letters to editors (Miall, 2007), papers (Geissbuehler and Lasser, 2013, Levine, 2009), editorials (anonymous, 2007), columns (Wong, 2011) and on numerous web pages. One of the recommendations is to use a color blindness simulator. Having a color vision deficiency myself, I cannot judge whether these tools work well. Nevertheless, a trial-and-error based approach seems rather inefficient. Instead, the use of (a number of) default color blind friendly palettes would be much more straightforward. For instance, green and magenta colors are the default choice for the production of color blind friendly overlays of fluorescence images. Below, I discuss a number of color palettes that are suitable for coloring graphical elements in plots. I think that people with a color vision deficiency would benefit from the implementation of these palettes in software for data visualization.
Qualitative color schemes
A quantitative color scheme is used when numbers need to be represented by colors. This conversion is done with a Look-Up Table (LUT). For more information on (colorblind-friendly) LUTs see this blog and this paper. Here, I talk about qualitative color schemes, which use colors to label different categories. The number of distinct categories define the number of unique colors that are needed. Ideally, these color can be distinguished by everybody.
For up to four categories, it is rather straightforward to come up with a set of colors that are easy to distinguish. Still, it does make sense to choose the colors from a color blind friendly color scheme. When 5-8 colors are needed to uniquely label different categories, it is a considerable challenge to find a suitable color palette. Beyond 8, it is close to impossible to find colors that can be readily distinguished. In these cases, alternative labeling methods are recommended. Below, several color blind friendly qualitative color schemes are described and four of those are shown in figure 1.
Color blind friendly palettes
Masataka Okabe and Kei Ito have proposed a palette of 8 colors on their website Color Universal Design (CUD). This palette is a “Set of colors that is unambiguous both to colorblinds and non-colorblinds”. The use of this palette is supported by others (Wong, 2011; Levine, 2009) and it is the default scale for the book “Fundamentals of Data Visualization” by Claus Wilke.
Martin Krzywinski has a website with 12- and 15-color palettes that offer more choices. Personally, I have difficulty with distinguishing several of these colors. Also, it is recommended to use no more than 8 different colors. Therefore, these palettes will not be taken along.
Paul Tol has created several qualitative color schemes that are color blind friendly. These palettes have 5-10 colors (including grey) and vary in darkness.
Figure 1: An overview of qualitative, color blind friendly palettes. The figure was produced with an R-script that defines and plots the palettes (doi: 10.5281/zenodo.3381072).
Choosing a color scheme
Which of the palettes is the best? This is hard to say for several reasons. Colors look different when printed, shown on a screen, or projected with a beamer. Next to this, size, structure and position of the objects will determine whether the categories can be distinguished. As a consequence, it is probably impossible to come up with a single universal color palette. I think that the palette designed by Okabe&Ito is a good first choice. Still, it is a good idea to see how different palettes perform when they are used in realistic data visualizations. As an example, figure 2 shows four plots in which the different color blind friendly palettes are used to label 6 lines.
Figure 2: The color palettes shown in figure 1 are used to uniquely label 6 different lines in a realistic data visualization. The graphs are with made with PlotTwist.
The palettes shown in figure 1 are implemented in the webtool PlotTwist (Goedhart, 2019). PlotTwist is a freely available online tool for plotting and annotating time-series data. It enables anyone to experiment with the color blind friendly palettes and apply them to lineplots. I encourage you to share your opinion on these (or any other) palettes and how they perform (especially if you have a color vision deficiency). To do so, you may leave a reply below or share your thoughts on twitter. Ultimately, I hope to see more data visualizations that pass a color blindness test with flying colors.
Recommendations
I will end with some recommendations aimed at improving graphs that use color:
-Use a color blind friendly palette by default.
-Use thick lines or large symbols to make it easier to correctly identify and map the color to a legend.
-In addition to colors, consider the use of patterns or labels to distinguish between categories.
We look back over the first 20 episodes of Genetics Unzipped to select some of our favourite bits that you might have missed.
There’s the tale of Esther Lederberg, whose contributions to science were overshadowed by her Nobel prize-winning husband, as well as an unexpected connection between the New England witch trials and Huntington’s disease.
Mary-Claire King describes how she stumbled into science, fell in love with genetics and went on to make groundbreaking discoveries. Finally, professional pyromaniac Fran Scott explains the importance of fire for human evolution.
If you enjoy the show, please do rate and review and spread the word. And you can always send feedback and suggestions for future episodes and guests to podcast@geneticsunzipped.com
The Company of Biologists’ journals – Development, Journal of Cell Science, Journal of Experimental Biology andDisease Models & Mechanisms – offer Travelling Fellowships of up to £3,000 to graduate students and post-doctoral researchers wishing to make collaborative visits to other laboratories. These are designed to offset the cost of travel and other expenses. There is no restriction on nationality.
They really are an amazing opportunity for ECRs to learn new things, meet new people and travel to new places.
The current round of Travelling Fellowships closes on 30 May (for travel after 11 July 2022)
Position Summary: The Marine Biological Laboratory seeks a motivated, creative and innovative Research Assistant or Research Associate to join the laboratories of Kristin Gribble and David Mark Welch in the Josephine Bay Paul Center for Comparative Molecular Biology and Evolution. Our research combines comparative genomics, biochemistry, and life history to study aging, maternal effects, and DNA damage prevention and repair using rotifers, a novel aquatic invertebrate model system for studies of aging, neurobiology, genome evolution, and ecology. The successful candidate will develop genome editing techniques in rotifers, including CRISPR/Cas9, as part of a broad initiative at the MBL to advance new aquatic and marine models for biological discovery. Research will take place in the Bay Paul Center, with extensive DNA sequencing and bioinformatic resources, and in the NSF-funded Genome Editing Facility in the Marine Resources Center, where MBL scientists are developing new genetic and genomic tools for a wide range of marine invertebrates. We invite individuals with experience in genome editing in other animals to join this expanding program.
Basic Qualifications: Research Assistant applicants should have a B.A., B.S., or Master’s degree in biology, cell/molecular biology, biochemistry, or a related field. Research Associate applicants should hold a Ph.D. or have commensurate laboratory experience. This position requires proficiency and previous experience in molecular biology, microscopy, microinjection, and CRISPR/Cas9 methodology. We are seeking an independent, organized, enthusiastic, and productive individual with robust problem solving skills. Excellent interpersonal skills, attention to detail, and a strong work ethic are essential. Position level and salary will depend upon education and experience.
Preferred Qualifications: The ideal candidate will have working familiarity with RNAi and transgenic protocols. Proficiency in bioinformatics is a plus. Previous experience in established animal model or in non-model systems is preferred.
Physical Requirements: Ability to work with biohazardous chemicals using proper personal protective equipment. Occasional lifting of heavy objects (<30 lbs).
Special Instructions: Please apply on the MBL website and submit the following three items with your application:
(1) Cover letter describing your experience, research goals, specific interest in joining our group, and what you would contribute to the project
(2) CV/resume
(3) Contact information for 3-4 references (Please do not send letters at this time; we will contact references directly).
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We look back over the first 20 episodes of Genetics Unzipped to select some of our favourite bits that you might have missed.