A postdoc position is available in the Percharde lab at the MRC LMS in London, to investigate novel aspects of nuclear structure and chromatin organisation during early embryo development.
Position title:
3-year fixed term postdoctoral position funded by the MRC
About the position:
The Percharde lab at the MRC London Institute of Medical Science (MRC LMS) is looking to recruit a talented and highly-motivated postdoc to join our group. The Chromatin & Development group is a recently-established team focused on understanding the molecular events surrounding cell fate choices during early development.
Our lab investigates mechanisms of chromatin regulation in early mammalian development. We also study how chromatin regulation and other mechanisms are important for transposable element (TE) expression and function.
In this project, the candidate will investigate the importance of nuclear and nucleolar structure and organisation during early mouse development. Focusing on specific key proteins of interest in the lab, they will use a combination of mouse models and mouse embryonic stem cells (ESCs) to investigate the importance of nuclear and nucleolar structure and chromatin in genome organisation and gene regulation during embryonic development. The project will involve techniques routinely employed in the lab including imaging, genome-wide chromatin and transcriptomic analysis, molecular embryology and CRISPR/Cas9 manipulation.
for more information about the lab. Closing date 11th Sept 2020
Candidate specifications:
Candidates should have a PhD or be in the final stages of completing one, and have a strong background in development, chromatin, or gene regulation, with this post ideally suiting someone with experience working with mouse embryos or ESCs looking to delve further into chromatin and developmental biology.
Apply:
For full details of this post and to complete an online application, visit: tinyurl.com/y5ngvdcc and upload your CV, the names and contacts of two scientific references, along with a cover letter stating why you are applying for this post (providing evidence against the requirements as per the Job Description and Person Specification).
The phrase “adjusting to the new normal” is a part of everyone’s life in one way or another, especially given our current global circumstances. Many in my circle are adjusting to facemasks, keeping physical distance (no friends/family meetups for months), constantly using hand sanitizers, cleaning surfaces at every turn/or use, ordering groceries online instead of going into stores, experimenting with all sorts of food recipes at home – breads galore, doing occasional pick-ups to support local restaurants, returning back to work with all the multiple safety measures in place, etc. etc. The list of what one should do can appear exhausting and without any light to hint at where the path/tunnel is let alone where it might end. It gets even more confusing when there is an abundance of mis-information, and deciphering out what is right and what should definitely be a no-no is all muddled up – sitting under a pile of all the other “must do’s” and “have-to-figure-it-outs.” This piece is just one snippet of a graduate student’s life.
There are many more gut-wrenching truths that the pandemic has brought to everyone’s surface; it has highlighted the myriad problems that exist in our systems globally and at every level. In the US, we have witnessed many horrifying deaths of innocent black lives, injustices faced by natives, mind-boggling rules against immigrants, cruel disregard towards lives of others and deeming such acts as a constitutional right. Sadly, this list goes on. Across the world, we have seen city closures so ill-planned that people are forced into the streets starving. We all have seen a severe lack of proper healthcare infrastructure and planning to combat the pandemic. It feels like wherever one turns to there are so many things that are clearly wrong, and they continue to stay wrong. I am still learning and figuring out how to take a positive and constructive stance on such critical issues. Right now, the only take I strongly hold is that we need to treat every human being with dignity and respect. There should be no room or allowance for mistreatment of others for some personal ego boost or the false belief that self is better than the rest. We need to do better as a community to ensure everyone feels safe, feel that they have a voice, and that people have mechanisms to access correct information in this age of information overload. I honestly right now don’t know what I should do to ensure all this, but I am going to work to get to that point. I am going to start by educating myself on all these matters that we collectively face.
Educating myself and trying to do better – this thought is my adjustment to normal over the years. I have previously, naively believed if I didn’t bother people and if I respected people, then I was doing OK. The religious upbringing I grew up with taught me that if you see a wrong there are three ways to approach it. The best way is to fix it by action, second best to voice out against it, third best is to believe in your heart of hearts that it is a clear wrong and make sure you don’t ever fall into doing it yourself. Up until high school I think I followed the first two, by action or by active voice against whatever my young self felt was wrong. Then upon migrating, and enveloped in the fear almost all outsiders face, I settled with number three. Maybe, falling into this third way was initially also a personal thing. I didn’t feel like I fit in or that I belonged, and so I didn’t want to make noise in a place that I wasn’t going to be in for long. Like most foreigners, I believed I would definitely go back home because the bubble of what I thought the US is burst soon after I got here. Only after a few years, and through identification of where I could finally fit, I was following number three purely out of fear. Fear that if I did something, it might either not be safe or it might affect my chances of being able to settle here permanently, and that would jeopardize the career and life I had begun to love. This was the normal I lived in for years.
The same way in which the “self” matures, the normal around me appears to constantly change, and I need to constantly adjust it to stay afloat. My dadiya (dad) would always tell me “Change is the only thing that is constant.” It was also to some degree his way of also comforting himself, because we both know how hard of a time each one of us has with change. My mommiya (mom) changing home décor after I got back from school used to be painful. Aside from that, my mommiya’s strength in the face of all challenges in life is inspirational to me. Her patience and understanding for my outside the typical lifestyle (for a desi girl) is my source of strength. When I started research, it was the first time I began to feel like I can have a home somewhere. Doing internships, working in a lab, and starting a PhD allowed me to dream about doing what I enjoyed. The reason it felt more special was because it got me excited about the thought of having my family together in one place eventually. However, like all sudden twists in life, this normal didn’t last very long. My dadiya very unexpectedly and suddenly passed away, while I tried to figure out my complicated visa situation.
There are many different facets to one’s life. While a part of me was starting to feel happy doing research and get excited about eventually going home and seeing all my family together. There was also another part of me that felt some days were just heavier. I felt stuck and I missed going home to my dadiya. When I first felt that my unconscious response was to separate myself from these emotions, and to keep myself busy to the point that I couldn’t think about them. But once I realized what I was doing, I started talking more about them instead. My dadiya and I would often talk about things we would do together when we met. Things that people take for granted – have a morning tea on the balcony, eat a meal together, whine about the same weather, go grab a coffee, go for a walk, and maybe on that walk go check out the library for our shared loved of all things written. When he suddenly passed away, it got really difficult to accept anything as normal. Figuring out how to adjust seemed just too unrealistic. I could write a whole journal on the moments after, and how they never truly end. I could talk about my guilt of wanting to keep my current life intact instead of being there with him in his last moments. I could talk about how my family never quite recovered, and how we keep a count almost of all the things he’s missing out on. I could talk about how staying home in this pandemic forced me to confront my reality and find my space. But it’s important to realize that while we cannot control many things in life that are painful and that hurt, there are some that we can: We can choose to care for each other, choose to respect each other. Choose to allow this fear of darkness/uncertainty to engulf us or we can stand our ground holding each other strong through these times.
Everyone is always adjusting to a new normal at some level, today we are in a time where we all collectively have to adjust to a new normal for a tomorrow that is there and for one that is safe for us all. We can all do our part. We must do our part!
In the latest episode of Genetics Unzipped, Kat Arney brings you exclusive excerpts from her new book, Rebel Cell: Cancer, evolution and the science of life, exploring where cancer came from, where it’s going, and how we might beat it.
Senior scientist position available in the Human Cells, Tissues, and Organoids (hCTO) Core of the Center of Regenerative Medicine at Washington University in St. Louis.
This position will serve as the Director of the hCTO Core and will be responsible for the running of the Core; this includes, but is not limited to: maintaining and differentiating human pluripotent stem cells, adopting and developing new differentiation and organoid culture methods, coordinating with researchers on the use of the hCTO Core, maintaining and operating core equipment, maintaining ESCRO protocols, and participating in group and one-on-one training sessions.
CRITICAL SKILLS/EXPERTISE: Analytical reasoning and problem-solving skills. Demonstrated working knowledge of standard laboratory policies, procedures and equipment. Ability to communicate in oral and written form with all levels of personnel and technical publications. Must be able to work well independently or as a team member. Must have experience maintaining and differentiating human pluripotent stem cells.
Interest in developing new stem cell methods and/or FACS experience would be a plus.
MINIMUM EDUCATION & EXPERIENCE: Requires PhD, M.D. or equivalent terminal degree and at least 3 years of postdoctoral or relevant industry experience.
To apply visit jobs.wustl.edu and search for job ID 48071.
Questions may be addressed to Angela Bowman, PhD, Executive Director, Center of Regenerative Medicine at abowman@wustl.edu
My name is Alicia Ugenti and I am an undergraduate from Amherst College studying Biology and Sexuality, Women’s, and Gender Studies. Last year, I took a course in Developmental Biology and for the past three years, I have conducted research in the lab of Katerina Ragkousi, with my time now culminating into a thesis for partial completion of a Bachelors of Arts in biology with honors. I am using the embryos of the sea anemone Nematostella vectensis to study how epithelia form during early development. With the ongoing lockdown due to the COVID-19 pandemic, my summer research stalled. The virtual SDB meeting provided me with the opportunity to broaden my knowledge about developmental biology and the recent breakthroughs in the field. As this was the first SDB meeting I attended, I expected to learn more about different developing organisms and hear first-hand from the people who are doing the research. I was very excited to learn about organoids, which is a new topic to me and one I hope to apply in my future career as a physician-scientist. This meeting has allowed me to consider my work in the future and prospects for which I am most passionate in developmental biology. Based on my research interests and my background, I have chosen to highlight the following talks:
In the Satellite Symposium: Emerging Leaders in Live Cell Imaging Approaches of Developmental Biology, Vanessa Barone from UC San Diego spoke about her research using sea stars and sea urchins to investigate the conserved connection between cell-cell contacts and nuclear β-catenin. Barone found that the number of large cell contacts positively correlates with nuclear localization of β-catenin levels in both sea stars and sea urchins. Erica Hutchins from the California Institute of Technology used chick embryos to investigate neural crest development and concluded that dynamic ribonucleoprotein granules found in the cell cytoplasm (P-bodies) control a developmental epithelial-to-mesenchymal transition program via post-transcriptional target degradation. Finally, Hidehiko Hashimoto from the University of Chicago discussed how the dynamic integration of cell-cell signaling, force generation, and tissue remodeling controls zippering and neural tube closure in ascidian embryos. Hashimoto found that during neural tube formation and closure, there is higher myosin activity along the entire Ne/Epi boundary (neural folds) ahead of the zipper and lower myosin behind the zipper.
During the Presidential Symposium, Nicole King from the University of California at Berkeley talked about how choanoflagellates can transition into an amoeboid state when under stress. Cells appear to retract the flagella and become motile in a myosin-dependent manner. This work implies that the evolution of animal amoeboid cells may have arisen from a stress-induced response that is hardwired in a post-transcriptional regulation program. Valentina Greco from Yale University discussed how modifying epithelial cell density in the skin of live adult mice triggers changes in the immune cell density, but not vice versa. This suggests that the immune tissue composition in the epidermis is influenced by epithelial cells. Epidermal immune cell patterning is organized and actively maintained in a tiling pattern. When LCs (Langerhans cells) are ectopically removed, neighboring epidermal LCs move into the emptied spaces and re-establish the pattern. The GTPase Rac1 is required for LCs to maintain their dendritic morphology, limited mobility, and tiling pattern. Overall, Greco’s lab discovered that during epidermal homeostasis, the spatial distribution of immune cells is highly regulated, at least in part by the epithelial stem cells.
I found the Special Interest Symposium: Confronting Bias in Scientific Culture, especially useful. Not only did it address how to pursue innovation in developmental biology,but it also encouraged me to think critically about my own role in changing the field and making it more inclusive. Mary Alice Scott from New Mexico State University spoke about cultural bias in science and how there are implicit lessons embedded in learning culture that are often unintended. Scott Gilbert from Swarthmore College spoke about the importance of establishing a culture of inclusive diversity and the importance of micro-affirmations, such as smiles, “good jobs,” engagement, and recognition of people who are under-represented inscience. Both speakers raised issues I have been thinking about especially while taking the Amherst College course ‘Being Human in STEM’. This course discusses the obstacles faced by STEM students of color and low-income and engages us in conversations about imposter syndrome, how our identity impacts our journey in STEM, and how important it is to make STEM inclusive starting at a young age.
Postdoctoral scientists presented their ground-breaking work in the Hilde Mangold Postdoctoral Symposium. A talk that particularly caught my interest was given by Zak Swartz, a postdoctoral fellow from the Whitehead Institute for Biomedical Research, who talked about the role of dishevelled in oocyte development of the sea star Patiria miniata. When dishevelled was knocked down, cells failed to gastrulate and upregulate the expression of WNT target genes. Swartz concluded that a cue at the vegetal pole of the oocyte must recruit Disheveled, which appears to colocalize with granules on Lamp1 positive endosomes.
In the Organoids: A Window to Developmental Processes session, we heard about the insights of organoids into liver and endometrium development. Sarah Saxton from the University of Washington showed how engineered liver tissues can replace damaged organs or compensate for the loss of function, and found that hepatoblast organoids can survive ectopic implantation and can produce human proteins that are measurable in the blood serum. This suggests that the grafts can integrate within the host vasculature and have good potential for a stable cell source for bioengineering. Mirna Marinic from The University of Chicago showed that using postpartum tissue is advantageous for forming endometrium organoids: it is technically easier to obtain, ethically less questionable and there are known pregnancy outcomes. Overall, personalized organoids engineered from different cell types can be used to study a variety of conditions.
In the Developmental Biology and Global Health session, we heard about the sexually transmitted ZIKA virus and a gene that causes infertility. Jennifer Watts, a Ph.D. candidate from Michigan State University showed how the sexually transmitted ZIKA virus affects inner cell mass fate in the zona-free blastocyst, thus making 2-cell embryos most susceptible. Maria Mikedis, a postdoctoral fellow from Whitehead Institute for Biomedical Research talked about a gene that causes infertility in mice. The DAZL protein (a member of the DAZ proteins found in men and associated with spermatogenic failure when not expressed) affects genes that are critical for spermatogonial development as well as broad regulators of fundamental cellular processes, specifically transcription and splicing.
Two talks in the Seeing is Believing: Imaging Revolution session highlighted cochlear and notochord development. Elizabeth Driver from the Matthew Kelley National Institute on Deafness and Other Communication Disorders at the NIH spoke about how Myosin II plays a critical role in the developing mammalian cochlea. She concluded that the coupling of Myosin II and E-cadherin acts in a complementary manner to control the size of hair cells, thus supporting cells and the junctions between them in order to ensure proper patterning of the cochlear sensory epithelium. Marissa Gredler from the Sloan Kettering Institute presented her work on notochord development, describing how, in the first phase of convergent extension, cells move to the surface where they undergo a mesenchymal-to-epithelial transition, and then move to the second phase where they undergo convergent extension characterized by mediolateral intercalation, cell mixing, and lateral protrusive activity.
Among the interesting talks in the Endless Forms Most Beautiful: Role of Biodiversity in Developmental Biology session, Ahmet Karabulut, a predoctoral researcher from the Stowers Institute for Medical Research, presented work on the venomous harpoons of the sea anemone Nematostella vectensis,showing that the harpoons are formed by two substructures: a shaft and a tubule. Interestingly, the harpoon discharge occurs in three stages: capsule explosion, shaft eversion, and tubule movements into the prey. The elastic energy is released by the shaft eversion and is transferred to the tubule as kinetic energy.
The Award Lectures were truly inspiring. Brigid Hogan, from Duke University and recipient of the FASEB 2020 Excellence in Science Award, spoke about the obstacles she had to overcome as a woman joining the field of developmental biology in an under-developed department. Hogan went on to discuss her research where she made important discoveries in mouse development and concluded that Pax6 is a highly conserved regulator of eye development. Cagney Coomer, from The University of Kentucky and recipient of the Society for Developmental Biology SDB Trainee Science Communication Award, spoke about her humanitarian work and is the founder of “Nerd Squad.” The missions of “Nerd Squad” are to empower brown and black girls interested in STEM, to design and develop culturally relevant STEM curricula, and to engage schools and the community in hands-on STEM activities. Celina Juliano, from the University of California Davis and recipient of the SDB – Elizabeth D. Hay New Investigator Award, spoke about her work on Hydra, discussing how conserved injury response transcription factors directly activate WNT signaling. Jo Handelsman, from the Wisconsin Institute for Discovery and the recipient of the Viktor Hamburger Outstanding Educator Prize, spoke about her report to President Obama about the need for more STEM and STEM-literate college graduates. In trying to create more STEM inclusive classes for undergraduates, Handelsman helped create “Tiny Earth”. Its goal is to inspire students about the power of science, teach them about bacterial cells, aid the antibiotic resistance crisis by allowing students to participate in antibiotic discovery, and make it cheaper and more efficient for pharmaceutical companies. Ray Keller, from the University of Virginia and recipient of the Developmental Biology-SDB Lifetime Achievement Award, spoke about his path in developmental biology, his work on morphogenesis, especially in the biomechanics of convergent extension during gastrulation of Xenopus. Finally, Claude Desplan, from New York University and recipient of the Edwin G. Conklin Medal, spoke about his work on Drosophila neural cells.
In my opinion, the online SDB conference this year was great in being so accessible to undergraduate students, as we were able to go back and re-watch the recorded talks. I would recommend undergraduates to attend SDB in the future as long as presentations are recorded – it really helps to be able to re-watch them carefully in order to fully absorb the information. I found that some speakers used specialized language that made the material difficult to understand, yet others were easy to follow with clearly communicating slides and summary pages. I found some acronyms hard to follow, which made following the talks difficult: writing out the meaning of acronyms on the slide would be very helpful. All in all, it was a great experience to watch people present their research and share their passion for their work. Lastly, it was refreshing to also have presentations on important conversations we should be having on how to improve STEM, such as enhancing diversity and making science courses more accessible and inclusive.
I would like to thank the SDB and the meeting organizers for making undergraduate registration free of charge this year, and for providing access to the online recorded presentations. I would also like to thank the Node and Aidan Maartens for his comments on this write-up.
There is a vacancy for a postdoctoral research fellow position at the Sars International Centre for Marine Molecular Biology (www.sars.no) in the research group headed by Dr. Pawel Burkhardt. The position is for a period of 3 years and is funded on the Sars Centre core budget. The Sars Centre belongs to the University of Bergen and is partner of the European Molecular Biology Laboratory (EMBL) (www.embl.de). The place of work will be at the Sars Centre. The preferred starting date is between October and December 2020.
About the project/work tasks:
The Burkhardt group combines comparative biological systems in the laboratory to understand when and how the first synapses and neurons evolved. The group is particularly interested in studying the origin and evolution of synaptic proteins. We are looking for a highly self-motivated and enthusiastic Postdoctoral Research Fellow with interests in evolutionary biology, neurobiology and cell biology. The project will focus on the functional characterization of synaptic protein homologs in choanoflagellates and ctenophores to better understand the evolution of first neuron-like cell types in animals. The successful candidate will undertake research with the possibility to use a variety of techniques, ranging from generating transgenic reporter lines, CRISPR/Cas9-mediated genome editing, super resolution immunofluorescence and electron microscopy to study synaptic protein homologs in choanoflagellates and/or ctenophores. The successful candidate will work in close association with the group leader and other lab members with the aim to contribute to the further development of the project in line with her/his interests.
Qualifications and personal qualities:
The applicant must hold a Norwegian PhD or an equivalent degree or must have submitted his/her doctoral thesis for assessment prior to the application deadline. It is a condition of employment that the PhD has been awarded
Strong motivation/enthusiasm to perform research at an internationally competitive level
Practical experience with CRISPR/Cas9-mediated genome editing and with different fluorescence imaging techniques is highly desirable
Specific experience with choanoflagellates or ctenophores is beneficial, but not essential
The ability to work both independently and to cooperate with others in a structured manner is essential’
Proficiency in both written and oral English
About the position of postdoctoral research fellow:
The position of postdoctoral research fellow is a fixed-term appointment with the primary objective of qualifying the appointee for work in top academic positions. The fixed-term period for this position is 3 years. Individuals may not be hired for more than one fixed-term period as a postdoctoral research fellow at the same institution.
Upon appointment, applicants must submit a project proposal for the qualifying work including a work schedule. It is a requirement that the project is completed in the course of the period of employment.
We can offer:
A professional, challenging and international working environment.
Well-equipped, modern laboratories and facilities
Salary at pay grade 59 (code 1352 / pay range 24, alternative 1) according to the state salary scale upon appointment. This constitutes a gross annual salary of NOK 523.200. Further promotions are made according to length of service. For particularly highly qualified applicants, a higher salary may be considered
Enrolment in the Norwegian Public Service Pension Fund
Detailed information about the position can be obtained by contacting: Group Leader Pawel Burkhardt, tlf.: +47 906 48 539, email: Pawel.Burkhardt@uib.no
The state labour force shall reflect the diversity of Norwegian society to the greatest extent possible. Age and gender balance among employees is therefore a goal. People with immigrant backgrounds and people with disabilities are encouraged to apply for the position.
The University of Bergen applies the principle of public access to information when recruiting staff for academic positions.
Information about applicants may be made public even if the applicant has asked not to be named on the list of persons who have applied. The applicant must be notified if the request to be omitted is not met.
Further information about our employment process can be found here.
A position for a postdoc is available in the Kebschull Lab at the Department of Biomedical Engineering at the Johns Hopkins School of Medicine in Baltimore, MD, for a start date after January 2021. We develop and apply cutting edge molecular and neuroanatomical tools to study how primordial circuits expanded in evolution to form the complex brains that exist today. We have a special focus on barcode sequencing-based high-throughput connectomics (BRICseq, MAPseq) and in situ sequencing, which we apply in the cerebellar nuclei and brain-wide in different vertebrates. Recent relevant papers include Kebschull et al. 2020 bioRxiv, Huang et al. 2020 Cell, Han et al. 2018 Nature, Kebschull et al. 2016 Neuron.
Candidates must hold a PhD degree (or equivalent) in neuroscience, biomedical engineering, molecular biology, or a related field. The ideal candidate should also have some bioinformatics skills and be passionate about brain mapping and evolution. We particularly encourage applications from any underrepresented or minority group.
Our lab is located on the School of Medicine Campus of Johns Hopkins University, surrounded by world-class neuroscience and biomedical engineering labs. We are committed to establishing a first-class, stimulating, and equitable environment in our new lab to allow you to flourish, achieve your goals, and further your career.
Qualified applicants should send a letter describing their current and future research interests, their CV, and names and contact details for three references to kebschull@jhu.edu. More information is available on https://www.kebschull-lab.org/.
Jaw joints, in most vertebrate animals that have them, form between a bone in the head called the quadrate and one in the mandible called the articular. The mandibles (lower jaw bone) of most vertebrates is compound, made up of fused bones, but we mammals are different. We have lots of different types of teeth that processes our food down by chewing. To help with this we evolved a novel jaw joint that allows for both lateral and front-to-back movements of the jaw against the head.
This new joint is between two bones that are nowhere near each other in non-mammals: the squamosal in the skull and the dentary in the mandible. In some mammals, such as humans, the squamosal is fused with other elements, making the temporal bone. In these species the jaw joint is also called the temporomandibular joint, or TMJ. Remember all those different fused bones in the mandible? Well we modern mammals only have the dentary left. As such, the dentary does many more jobs in mammals than it does in non mammals. In non-mammals the dentary hold the teeth, while in mammals it additionally makes the jaw joint, and accts as the muscle attachment site for the muscles of the jaw.
So where have all the other bones gone? Some appear to have been lost, but other have been repurposed and are now part of hearing apparatus. Remember the quadrate and articular that make the jaw joint in most jawed vertebrate? We mammals still have those bones, but we call them the malleus and incus. Alongside the stapes these bones form the middle ear, are the smallest bones in the body, and transmit sound from the air and through to the sensory cells in the inner ear.
How do we know that parts of the mammal middle ear are homologous to the jaw joint of non-mammals? Well, first fossils: this transition is a classic transitional series. 250 million years ago there were stem-mammals that had double jaw joint, and who’s primary jaw joint became involved in hearing (Morganucodon is a textbook example). But we are not palaeontologists, and so we look to another source of evidence: developmental biology. We know that the middle ear bones of mammals develop as part of the mandible, and only separate after the secondary jaw joint forms (Anthwal et al 2017, Urban et al 2017). However when the jaw joint forms differs across the major groups of mammals.
Schematic comparison of thhe jaw and ear in a non-mammal gecko, stem-mammal fossil Morganucodon, and mammal opossum. From https://elifesciences.org/articles/57860
Comparing living mammal groups
There are three living groups of mammals, which can be sorted into two subclasses. The therian mammals are marsupials (such as kangaroos, wombats and opossums) and eutherians (aka placentals, though marsupials also have placentas), while the monotremes occupy the other subclass. Living monotremes are the five species of echidnas and one species of platypus. They are now found only in Australia and New Guinea. Monotremes retain a number of more basal characters, which include reproduction via egg laying, a sprawling gait, and a cloaca (a single opening for the reproductive defecatory and urinary systems). They also lack nipples, and instead secrete milk from specialised mammary patches. The young then suck up this milk from the skin on the mother,
Eutherian (placental) mammals have a longer foetal period development than marsupials and egg laying monotremes. So, our jaw joint and middle ear develops either in utero or shortly after birth. In contrast, monotremes and marsupials are born relatively early in development, so early in fact that they haven’t made their mammalian jaw joint yet. So how do they feed? The answer, which we investigate in our new paper recently published in eLife, is via their middle ear bones, which are still part of the mandible at this developmental stage.
Using archived and new samples to take an evo-devo approach
Fossils indicate that the final steps of middle ear evolution happened independently in monotremes compared to eutherians and marsupials, so we thought that monotremes might use their middle ear differently at hatching. The problem then was how to look at monotreme young, since they’re hardly a model organism. We do have access to an established lab model marsupial, the opossum Monodelphis domestica, thanks to collaboration with another of my mentors, Karen Sears at UCLA, but monotremes are harder to study. Of the extant monotremes, only the short beaked echidna is not CITES protected, and even that species isn’t amenable to lab work.
Ideally we wanted to look at both extant groups of living monotremes, platypus and echidna. To do so we made use of work done in the past. DMS Watson and others had studied platypus and echidna young in the early 20th century and investigated their cranial development by making histological sections. These slides still exist as part of the Hill Embryology Collection at the Museum für Naturkunde in Berlin, and in the collection of the Zoological Museum in Cambridge. So my PI at King’s College London Abbie Tucker went to Berlin to look at and image the slides there, and we both took turns visiting Cambridge.
Histological sections showing platypus middle ears, from the Cambridge and Berlin museums. These sections were first described by Watson in 1915 (10 day and 80 day) or Green in 1937.
We compared these samples from early last century with lab derived developing mice and new born opossums. Anatomically, you can see big differences between each group, including between the marsupials and monotremes. Monotremes have a tiny incus compared to the malleus. In the youngest animals from the museums we were surprised to see the incus fused to the petrosal in the head. Later on they become separated, but they remain articulated, and these articular surfaces remain cartilaginous when the rest of the bone has ossified.
The opossum and eutherian mammals however have a large incus. In opossums the incus appears to be held in place against the head, or possibly cushioned, by a special mesenchyme rich in extra cellular versican. This mesenchyme is missing from eutherians. We think this mesenchyme allows marsupials to suckle before the jaw joint forms, and that this is a different strategy to the fusion seen in monotremes.
Exploring monotremes futher
The mandibular fusion in monotremes was pretty interesting, as the incus and petrosal developed from distinct parts of the embryo. Mouse and chick studies show that the incus/quadrate forms from first pharyngeal arch neural crest derived ectomesenchyme, whereas the petrosal is mostly mesoderm with a small component of second pharyngeal arch neural crest. So we wanted to look at the monotremes in more detail. What is the developmental anatomy of this fusion? How does the separation occur? To get at these questions we were lucky to collaborate with Marilyn Renfree and Jane Fenelon at the University of Melbourne, and Steve Johnston at the University of Queensland in Australia to look at echidnas at the youngest stages. Marilyn and her team have had access tot a breeding colony of echidnas at the Currumbin WIldlife Sanctuary in Queensland. Look out for their exciting work on in egg and early hatching echidnas.
With these fresh samples we were able to look at protein expression by immunohistochemistry in developing post-hatching monotremes for the first time.
Alcian blue staining (left) and immunohistochemistry in Echidna middle ear at day 0. The cartilages of the middle ear of newly hatched monotremes is fused to the skull between the incus and the petrosal.
We found that the early fusion visible in histology was confirmed by expression of SOX9, a transcription factor that drives cartilage development. In older samples, we also found nuclear beta catenin in the region that would separate the incus and petrosal. Mouse studies show that nuclear beta catenin down regulates cartilage during joint formation. When considered alongside and the cartilaginous articular surfaces we see in the older juvenile specimens we studied form the museums, this nuclear beta catenin expression suggests that a joint forms between the incus and petrosal that may be functional in the feeding process.
Next we looked for any evidence of fusion in mice, taking advantage of genetic reporter lines unavailable in monotremes and marsupials. In simple histology staining, we never see fusion of the incus and petrosal. However, to our surprise, Sox9 Cre reporter mice show that the precursors cells of these two elements are in fact “fused”. So it seems that in mice the fusion between the incus and petrosal is early and transient. We also found expression of a joint marker – Gdf5- between the incus and petrosal in mouse embryos. We then took advantage of Mesp1Cre reporter mice, which labels mesoderm tissue, to test where the fusion in Sox9 expression cells occurred. This line told us that the fusions, at least in mice, occurred between the first arch neural crest of the incus and the second arch crest part of the petrosal.
So what does this all mean?
First, we found that marsupials and monotremes have different anatomical strategies for feeding when they are first born – fusion in monotremes versus bracing or cushioning in marsupials. Second, despite the fact that they never need to have a functioning non-mammal jaw joint, mice have a similar transient articulation between their incus and skull to monotremes. This is despite the independent acquisition of the definitive middle ear form in these groups. Given that both mice and echidnas have an articulation, it seems parsimonious that the common ancestor of therian and monotreme mammals (whose middle ear was still attached to their mandible) would have had an incus petrosal joint. We can therefore speculate that this was early in their life before the secondary jaw joint had fully grown.
In adult mammals the middle ear is connected to the mandible ligaments. Developmental defects in the ear and jaw are closely associated. Jaw trauma can lead to knock-on effected in the middle ear. By studying the evolution and development of the jaw and ear, we can also get a better understanding of these connections.
Position Summary:
The MBL is seeking a candidate for the position of Postdoctoral Scientist in the laboratory of Dr. Blair Paul to investigate physical interactions among uncultivated microbial symbioses from aquatic environments. For more information about our lab’s work, see https://www.mbl.edu/jbpc/staff/bgpaul/. This project is funded by The Betty and Gordon Moore Foundation’s Symbiosis in Aquatic Systems Initiative and offers opportunities to collaborate with the labs of co-investigators at UC Berkeley, UC San Diego, and UC Santa Barbara. The ideal candidate will apply existing skills in biochemistry and genetics to assist with development of a high-throughput workflow for cell isolation. This research will involve a synergistic combination of experimental biology and bioinformatics to examine the molecular interface between microbial symbionts and their hosts. We enthusiastically encourage individuals from backgrounds that are underrepresented in STEM fields to apply for this opportunity.
Additional information: The position is for two years with potential for extension, contingent on performance and funding. Salary will be commensurate with experience and qualifications. For more information about MBL and living on Cape Cod, please visit: https://www.mbl.edu/hr/employment/our-community/.
Basic qualifications: A Ph.D. in biology, microbiology, molecular biology, biochemistry, or a related field is required.
Preferred qualifications: Experience in the following areas is desirable: protein biochemistry, microbial cultivation, and/or bacterial or archaeal genetics.
Instructions: Please apply on the MBL website and provide the following required documents: (1) a cover letter describing your interests, skills, and prior research experience, including any specific experience with the job responsibilities listed above; (2) a curriculum vitae/resume; and (3) the names and contact numbers of three persons who can be contacted for letters of reference, at least one of whom must have acted as your supervisor in a previous research position.
#Biotechnology #Imaging #Arthritis research # Drug discovery # Vienna # Machine learning #Cell differentiation assay #Organ-on-a-chip #Biotechnology #Microfluidic #EVOS7000 #personalized medicine #Automation #Liquid Handling #cell biology #Molecularbiology
Pregenerate is a young startup based on the lively Vienna Biocenter Campus surrounded by 12 other start up companies. At Pregenerate we are revolutionizing arthritis treatment with our organ-on-a-chip platform. This technology will ultimately allow us to stratify patients into targeted treatment subgroups, and even to tell each clinical patient what the best treatment is for their specific arthritis needs directly. Our device is also poised to save pharmaceutical companies billions of dollars and improve the success rates of their drugs to market, partly because we can use human cells to replace animal testing in pharmaceutical research for arthritis treatments.
Rosser, J. et al. Microfluidic nutrient gradient-based three-dimensional chondrocyte culture-on-a-chip as an in vitro equine arthritis model. Mater Today Bio4, 100023, doi:10.1016/j.mtbio.2019.100023 (2019).
Vinatier, C. & Guicheux, J. Cartilage tissue engineering: From biomaterials and stem cells to osteoarthritis treatments. Ann Phys Rehabil Med59, 139-144, doi:10.1016/j.rehab.2016.03.002 (2016).
Haltmayer, E. et al. Co-culture of osteochondral explants and synovial membrane as in vitro model for osteoarthritis. PLoS One14, e0214709, doi:10.1371/journal.pone.0214709 (2019).
Please send the application with CV, academic record and coverletter to faheem@pregenerate.net
Molecular Biologist – technician
Establishment of Gene expression analysis at Pregenerate. Your aim will be to establish robust pipeline for analyzing responses to various medications to indicate the best treatment for arthritis on an individual patient level. Future work will include automating the system using a liquid handler.
Your talents and abilities:
M. Sc. in Life Sciences
Strong expertise in molecular biology (RNA extraction, qPCRs, Immunohistochemistry,…)
Tissue Culture experience
Skills in Excel and R programming would be advantageous
Good organizational skills
Enthusiasm for personalized medicine
Preferred starting date is 1st September, 2020
Imaging specialist
Leading the development of image analysis section at Pregenerate using Organ-on a chip technology. Your aim will be to establish and automated image analysis system to visualize the response of various medication in a 3D microfluidic system.
Your talents and abilities:
PhD in Life Sciences (M Sc. considered)
Strong expertise in imaging and imaging analysis
Image J programming a significant advantage
Experience with Confocal imaging and EVOS 7000
Image automation experience
Experience with microfluidics would advantageous
Skills in Excel and R programming would be advantageous
Project management
Enthusiasm for personalized medicine
Preferred starting time is September / October 2020
Our lab investigates mechanisms of chromatin regulation in early mammalian development. We also study how chromatin regulation and other mechanisms are important for transposable element (TE) expression and function.
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In the latest episode of Genetics Unzipped, Kat Arney brings you exclusive excerpts from her new book, Rebel Cell: Cancer, evolution and the science of life, exploring where cancer came from, where it’s going, and how we might beat it.
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