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Postdoctoral Position to study roles of extracellular microenvironment in cardiovascular development

Posted by , on 9 November 2017

Closing Date: 15 March 2021

The composition of extracellular microenvironment is dynamically regulated in time and space during embryonic development, and our lab discovered that cell-type specific expression of the extracellular matrix protein fibronectin is essential for mammalian embryogenesis. Furthermore, we found that fibronectin regulates distinct morphogenetic processes in cell type-specific manner, and functions both in cell-autonomous and non cell-autonomous manner. We are searching for a motivated postdoctoral researcher to uncover differences in the mechanisms by which cell-autonomous and non cell-autonomous fibronectin signals to cells and regulates cell fate decisions. The successful applicant will apply state-of-the art confocal and super-resolution microscopy techniques, utilize mouse genetics, CRISPR, and global profiling of gene expression and signaling pathways to uncover the mechanisms, by which extracellular microenvironment guides morphogenetic programs. Our lab is located in the heart of Philadelphia, USA. For further information about our lab and publications, please visit our lab’s website: http://www.jefferson.edu/university/research/researcher/researcher-faculty/astrof-laboratory.html
To apply, please send a letter of interest detailing your expertise, CV and names and contact information of three references to sophie.astrof@gmail.com

As an employer, Jefferson maintains a commitment to provide equal access to employment.  Jefferson values diversity and encourages applications from women, members of minority groups, LGBTQ individuals, disabled individuals, and veterans.    

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Addgene Resources to Grow Your Developmental Biology Toolkit

Posted by , on 8 November 2017

Addgene is a global, nonprofit repository that was created to help scientists share plasmids. Before we go over the developmental biology resources available at Addgene, here’s a little background on our organization. Our mission is to accelerate research and discovery by improving access to useful research materials and information. Labs deposit plasmids with Addgene at no cost, and we handle storage, distribution, and record keeping. Researchers can request plasmids and, in some cases, ready-made lentivirus and AAV, from our collection, and we coordinate Material Transfer Agreements to facilitate easy sharing.

We also provide numerous educational resources on our blog and website. Our Plasmids 101 and CRISPR 101 blog series were designed to help scientists of all levels learn more about molecular biology, cloning, genome engineering, and other popular technologies. To make it easy to find plasmids for a given purpose, we provide curated pages on our website for various plasmid collections like CRISPR, stem cells, cancer, and fluorescent proteins. Addgene’s technical support team also provides scientists with real-time plasmid troubleshooting. By providing these services, Addgene’s goal is to create a lasting resource for research and discovery around the world.

Developmental biologists have deposited many of Addgene’s most popular plasmids. I’ll cover the general collections most relevant to developmental biology and also highlight a few standouts from our collection.

Stem Cell Tools

Our stem cell collection is a true Addgene strength. We have many plasmids that cover methods for iPS cell generation – retroviral, lentiviral, adenoviral, episomal and non-viral methods. We also distribute plasmids for direct differentiation and transdifferentiation. These plasmids are conveniently organized on our Stem Cell Collection page. Keep an eye out for the blue flame plasmids – these each have been requested over 100 times and have proven useful for many researchers!

  Plasmid spotlight: Andras Nagy Piggybac reprogramming plasmids

Lentiviral and retroviral reprogramming methods carry the caveat of insertional mutagenesis, while plasmid and adenoviral reprogramming methods suffer from lower efficiency. Woltjen et al. created a Tet-inducible reprogramming system using the Piggybac transposase. This system allows you to easily reprogram fibroblasts into iPS cells using only plasmids – there’s no need to prepare or deliver virus to your cells. Instead, you co-express PB-TET-MKOS containing the four Yamanaka factors, PB-CA-rtTA Adv containing the rtTA Tet transactivator, and a plasmid containing the Piggybac transposase (available from Transposagen and others.) Doxycycline treatment then turns on MKOS expression, promoting reprogramming. Once reprogrammed lines have been isolated, transient expression of Piggybac transposase will remove the MKOS transgene from the genome.

CRISPR Plasmids for Use With Developmental Models

Addgene’s CRISPR collection also has resources for scientists interested in developmental biology. On our CRISPR landing page, you can find plasmids sorted by model organism or system. In addition to our many mammalian expression plasmids, we have plasmids available for common developmental models like Drosophila, C. elegans, Xenopus and zebrafish. Addgene also maintains a list of Pre-designed gRNAs that have been used in previous publications, and you can easily search the table for your favorite gene. We also encourage you to deposit your own gRNA plasmids.

  Plasmid spotlight: Leonard Zon Zebrafish CRISPR plasmids

Zebrafish have proven very amenable to CRISPR genome engineering, and the Zon lab Gateway constructs can help you to knock out your gene of interest in a tissue-specific manner. Their Tol2 based system enables you to examine mosaic disruption of your gene in F0 embryos or to generate stable tissue-specific knockout lines. All four plasmids from this publication have earned blue flames for 100+ requests! To use this system, you’ll combine Gateway destination vector pDestTol2pA2-U6:gRNA or pDestTol2CG2-U6:gRNA with a middle entry vector containing Cas9 (e.g. pME-Cas9). You’ll also need a 5’ entry vector containing your tissue-specific promoter and a 3’ entry vector with a polyA sequence, both of which can be obtained from the Tol2kit. A Gateway reaction will bring the pieces together, allowing you to examine the effects of gene knockout in a specific tissue. A detailed protocol is available from the Zon lab on the plasmid pages of each Addgene plasmid.

Cre-Lox Systems for Spatio-Temporal Control of Gene Expression

If you’re using Cre-lox recombination to turn gene expression ON or OFF, chances are Addgene has plasmids you can use. In addition to standard Cre recombinase, we also provide inducible, promoter-regulated, and optimized Cres, to name a few. Cre-dependent vectors expressing fluorescent proteins or luciferase are also available. FLEx (FLip-Excision) vectors, which conditionally turn off one gene and activate another, are available from many Addgene depositors. PhiC31 recombinase and other non-Cre recombinases are available for use in Drosophila.

  Plasmid spotlight: Connie Cepko pCAG-ERT2CreERT2 plasmid

This plasmid expresses CreERT, or tamoxifen-inducible Cre, in a mammalian expression system. In cell lines transfected with this plasmid, tamoxifen will activate Cre, allowing removal or inversion of a floxed gene of interest. This plasmid has been requested over 1100 times, showing its versatility and applicability to many kinds of studies.

Lineage tracing plasmids make up another exciting mini-collection at Addgene. Brainbow is a combinatorial Cre-lox based system that colors single cells with as many as 90-160 different colors. Many of Addgene’s Brainbow plasmids have blue flames. Although originally developed for neuronal mapping, these plasmids have been adapted for lineage tracing. Multibow plasmids adapted from the Brainbow system for use in zebrafish create unique “barcodes” allowing researchers to track individual cells and their clonal progeny.

It’s impossible to cover all of the resources available at Addgene in one blog post, so we encourage you to take a look at our website. If you’re looking for plasmids from a specific publication, start by searching for the paper’s corresponding author to see if she or he has deposited with us. You can also sign up for Addgene Alerts for your favorite PIs and you’ll get emails whenever new plasmids are available from their labs. If you have trouble finding what you need, or you’d like us to reach out to a potential depositor, feel free to email us at help@addgene.org. We also encourage you to deposit your own plasmids thereby making them easily accessible to other members of the research community.

Mary Gearing is a Scientist at Addgene. She enjoys developing educational content to help scientists learn more about molecular biology. Follow her on Twitter @megearing.

Addgene Resources

Stem Cell Collection

CRISPR Collection

List of Validated gRNAs

Cre-Lox Collection

Addgene Blog

Plasmids 101: FLEx Vectors

Cre-ating New Methods for Site-Specific Recombination in Drosophila

References

piggyBac transposition reprograms fibroblasts to induced pluripotent stem cells. Woltjen K, Michael IP, Mohseni P, Desai R, Mileikovsky M, Hamalainen R, Cowling R, Wang W, Liu P, Gertsenstein M, Kaji K, Sung HK, Nagy A.  Nature. 2009 Apr 9;458(7239):766-70. doi: 10.1038/nature07863. PMID: 19252478

A CRISPR/Cas9 Vector System for Tissue-Specific Gene Disruption in Zebrafish. Ablain J, Durand EM, Yang S, Zhou Y, Zon LI.  Dev Cell. 2015 Mar 4. pii: S1534-5807(15)00075-1. doi: 10.1016/j.devcel.2015.01.032. PMID: 25752963

High-Efficiency FLP and PhiC31 Site-Specific Recombination in Mammalian Cells. Raymond CS, Soriano P. PLoS ONE. 2007 Jan 17;2(1):e162. PMID: 17225864

Multiple new site-specific recombinases for use in manipulating animal genomes. Nern A, Pfeiffer BD, Svoboda K, Rubin GM. Proc Natl Acad Sci USA. 2011 Aug 23;108(34):14198-203. doi: 10.1073/pnas.1111704108. PMID: 21831835

Controlled expression of transgenes introduced by in vivo electroporation. Matsuda T, Cepko CL. Proc Natl Acad Sci U S A. 2007 Jan 16;104(3):1027-32. PMID: 17209010

Improved tools for the Brainbow toolbox. Cai D, Cohen KB, Luo T, Lichtman JW, Sanes JR. Nat Methods. 2013 May 5;10(6):540-7. doi: 10.1038/nmeth.2450. PMID: 23817127

Multibow: digital spectral barcodes for cell tracing. Xiong F, Obholzer ND, Noche RR, Megason SG. PLoS One. 2015 May 26;10(5):e0127822. doi: 10.1371/journal.pone.0127822. eCollection 2015. PMID: 26010570

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Silencing transposons during epigenetic reprogramming

Posted by , on 8 November 2017

Production of proteins from transposons (red). DNA shown in blue.

Molecules called endosiRNAs help us avoid genetic chaos, according to a new study from a team at the Babraham Institute. Much of the human genome contains pieces of DNA called transposons, a form of genetic parasite. When active, transposons can damage genes so it is important to keep them inactive. At a certain point early in the human life cycle controlling transposons is particularly difficult. This latest research, published in Cell Stem Cell reveals how endosiRNAs keep our genes safe during this vulnerable stage.

Transposons, also called transposable elements, are ancient viruses that have become a permanent part of our genes. Around half of the human genome is made of transposons, many are damaged, but some can become active. Active transposons can be harmful because they move about the genome. When transposons move they can damage genes, leading to genetic illnesses and playing a part in some cancers.

Chemical markers in DNA called methylations can keep transposons inactive. Cells often use methylations to inactivate pieces of DNA, whether they are genes or transposons. Yet, in each new generation most methylations are temporarily erased and renewed by a process called epigenetic reprogramming. This means that, during sperm and egg production there is a short time when methylations do not control transposon activity, leaving them free to damage genes and shuffle DNA.

The new findings show that transposons become active when cells erase DNA methylation and they are shut down by the endosiRNA system. Just like active genes, active transposons produce messages in the form of RNA molecules, which have many similarities to DNA. The study reveals that cells can detect these transposon RNA messages and use them to create specific endogenous small interfering RNAs (endosiRNAs). The endosiRNAs then act like a trap allowing a protein called Argonaute2 (Ago2) to seek and destroy transposon messages before they cause any harm.

Speaking about the research, lead author on the paper, Dr Rebecca Berrens, said: “Epigenetic reprogramming plays a vital role in wiping the genome clean at the start of development, but it leaves our genes vulnerable. Understanding the arms race between our genes and transposon activity has been a long-running question in molecular biology. This is the first evidence that endosiRNAs moderate transposon activity during DNA demethylation. EndosiRNAs provide a first line of defence against transposons during epigenetic reprogramming.”

The effects of active transposons vary, often they have no effect, only occasionally will they alter an important gene. Yet, transposons can affect almost any gene, potentially leading to different kinds of genetic disease. Studying the control of transposons, adds to our understanding of the many ways that they can impact on human health.

This work highlights that a transposons often sit within genes and are read in the opposite direction to the surrounding gene. It is this arrangement that allows cells to identify RNA messages from transposons. RNA messages read from the same piece of DNA in opposite directions are complementary, meaning they can join to form a structure called double-stranded RNA (dsRNA), which initiates the creation of endosiRNAs.

Senior scientist on the paper, Professor Wolf Reik, Head of the Epigenetics Laboratory at the Babraham Institute, said: “Transposons make up a large part of our genome and keeping them under control is vital for survival. If left unchecked their ability to move around the genome could cause extensive genetic damage. Understanding transposons helps us to make sense of what happens when they become active and whether there is anything we can do to prevent it.”

Much of this research was carried out using embryonic stem cells grown in the lab, which had been genetically modified to lack DNA methylations. Natural epigenetic reprogramming happens in primordial germ cells, the cells that make sperm and eggs, but these are harder to study. The researchers used primordial germ cells to verify the key results from their study of stem cells.

 

Notes:

Publication Reference

Berrens, RV., Andrews, S., Spensberger, D., Santos, F., Dean, W., Gould, P., Sharif, J., Olova, N., Chandra, T., Koseki, H., von Meyenn, F., Reik, W.. An endosiRNA-based repression mechanism counteracts transposon activation during global DNA demethylation in embryonic stem cells. Cell Stem Cell
DOI: http://dx.doi.org/10.1016/j.stem.2017.10.004

Research Funding
This work and the researchers that contributed to it were generously supported by SNSF, Gates Cambridge Trust, BBSRC (Epigenetics Institute Strategic Programme Grant), Wellcome Trust, EU BLUEPRINT and EpiGeneSys

Image Credit
Credit: R. Berrens
Header – Image of fluorescently labelled embryonic stem cells. These cells have been modified to mimic the effects of epigenetic reprogramming. DNA in the cells is marked in blue. Red indicates cells that contain active transposons.
Embedded – Graphical abstract of the key findings from the paper. The opposing directions of a transposon and a gene result in double stranded RNA that can be used to produce endosiRNA to prevent transposon activation. Credit: Veronique Juvin

Animal Statement:
As a publicly funded research institute, the Babraham Institute is committed to engagement and transparency in all aspects of its research. Animals are only used in Babraham Institute research when their use is essential to address a specific scientific goal, which cannot be studied through other means. The main species used are laboratory strains of rodents, with limited numbers of other species. We do not house cats, dogs, horses or primates at the Babraham Research Campus for research purposes.

Samples of primordial germ cells were collected from C57Bl/6J transgenic mice at embryonic day 13.5 and 14.5. The use of animals in this study was performed in accordance with the Animal (Scientific Procedures) Act 1986, and regulated by the Babraham Institute Animal Welfare and Ethical Review Body (AWERB). Experiments were planned and designed in accordance with the 3Rs.

Please follow the link for further details of the Institute’s animal research and our animal welfare practices: http://www.babraham.ac.uk/about-us/animal-research

About the Babraham Institute:
The Babraham Institute receives strategic funding from the Biotechnology and Biological Sciences Research Council (BBSRC) through an Institute Core Capability Grant to undertake world-class life sciences research. Its goal is to generate new knowledge of biological mechanisms underpinning ageing, development and the maintenance of health. Research focuses on signalling, gene regulation and the impact of epigenetic regulation at different stages of life. By determining how the body reacts to dietary and environmental stimuli and manages microbial and viral interactions, we aim to improve wellbeing and support healthier ageing.

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Scientific Copy Editor

Posted by , on 8 November 2017

Closing Date: 15 March 2021

Cambridge, United Kingdom

 

The Company of Biologists (biologists.com) is looking to recruit a Scientific Copy Editor to work across our portfolio of five life-science journals, with a particular focus on Journal of Experimental Biology. This full-time position is available for two years initially. The role entails copyediting articles to a high standard, compiling author corrections, overseeing the journal production process, and liaising with authors, academic editors, external production suppliers and in-house staff to ensure that articles are published in a timely and professional manner.

Candidates should have a degree (ideally a PhD) in a relevant scientific area, and previous copyediting experience is strongly preferred. Additional requirements include excellent literacy skills, high attention to detail, a diplomatic communication style, good interpersonal and IT skills, a flexible approach and the ability to work to tight deadlines.

The position represents a unique opportunity to gain experience on our highly successful life-science journals and offers an attractive salary and benefits. The position will be based in The Company of Biologists’ attractive modern offices on the outskirts of Cambridge, UK.

The Company of Biologists (biologists.com) exists to support biologists and inspire advances in biology. At the heart of what we do are our five specialist journals – Development, Journal of Cell Science, Journal of Experimental Biology, Disease Models & Mechanisms and Biology Open – two of them fully open access. All are edited by expert researchers in the field, and all articles are subjected to rigorous peer review. We take great pride in the experience of our editorial team and the quality of the work we publish. We believe that the profits from publishing the hard work of biologists should support scientific discovery and help develop future scientists. Our grants help support societies, meetings and individuals. Our workshops and meetings give the opportunity to network and collaborate.

Applicants should send a CV to recruitment@biologists.com, along with a covering letter that summarises their relevant experience, why they are enthusiastic about the role, and their current salary.

All applications should be received by 27 November, although late applications may still be considered.

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How do primary cilia control the activity of stem cells in the developing cerebral cortex?

Posted by , on 7 November 2017

Closing Date: 15 March 2021

 

SUPERVISORS: Dr Thomas Theil and Dr Pleasantine Mill

PROJECT SUMMARY
This project will dissect how cell signalling via the primary cilium coordinates the activity of neural stem cells during the development of the cerebral cortex. Proliferation and differentiation of cortical stem cells are tightly controlled processes. Changes in these parameters can have profound effects on cortical size and are thought to underlie cortical malformations in human disease and the expansion of the human cerebral cortex during evolution.

To investigate roles of primary cilia in cortical stem cell development, the project will employ Inpp5e mutant mice which display an elongated, folded cerebral cortex. Using a combination of in utero electroporation with super resolution and live imaging of primary cilia dynamics in the developing brain the project aims to understand how primary cilia control the signalling required to determine the balance between stem cell proliferation and neurogenesis and how cilia determine the asymmetric inheritance of cell fate determinants These analyses will be a vital step towards gaining a comprehensive understanding of how cilia coordinate the proliferation of cortical stem cells in health and in ciliopathies, human syndromes caused by defects in cilia structure and/or function.

STUDENT TRAINING
The PhD student will be closely integrated into the Theil and Mill research groups which have overlapping and complementing interests in cortical development and primary cilia. The student will benefit from the excellent research environment and the unique research infrastructure including state of the art animal and super-resolution imaging facilities at the Centre for Discovery Brain Sciences and at the Institute for Genetics and Molecular Medicine at the University of Edinburgh.

FUNDING NOTES

Applications for BBSRC EASTBIO studentships are invited from excellent UK students (and EU citizens if they meet UK Research Council residency criteria) with at least a BSc (Hons) 2.1 undergraduate degree.

MORE INFORMATION

https://www.findaphd.com/search/ProjectDetails.aspx?PJID=90134

e-mail: thomas.theil@ed.ac.uk

HOW TO APPLY?

Applications, and curriculum vitae should be sent to PGR student team at RDSVS.PGR.Admin@ed.ac.uk

APPLICATION DEADLINE: 4th December 2017.

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Four Year (1+3) PhD Programme in Stem Cell Biology & Medicine

Posted by , on 7 November 2017

Closing Date: 15 March 2021

Department/Location: Wellcome Trust – Medical Research Council Cambridge Stem Cell Institute
Studentships starting October 2018

 

Stem Cell Biology
Stem cells are defined by the dual capacity to self-renew and to differentiate. These properties sustain homeostatic cell turnover in adult tissues and enable repair and regeneration throughout the lifetime of the organism. In contrast, pluripotent stem cells are generated in the laboratory from early embryos or by molecular reprogramming. They have the capacity to make any somatic cell type, including tissue stem cells.

Stem cell biology aims to identify and characterise which cells are true stem cells, and to elucidate the physiological, cellular and molecular mechanisms that govern self-renewal, fate specification and differentiation. This research should provide new foundations for biomedical discovery, biotechnological and biopharmaceutical exploitation, and clinical applications in regenerative medicine.

Cambridge Stem Cell Community
The University of Cambridge is exceptional in the depth and diversity of its research in Stem Cell Biology, and has a dynamic and interactive research community that is ranked amongst the foremost in the world. By bringing together members of both the Schools of Biology and Medicine, this four year PhD programme will enable you to take advantage of the strength and breadth of stem cell research available in Cambridge. Choose from over 50 participating host laboratories using a range of experimental approaches and organisms.

Programme Outline
During the first year students will:

  • Perform laboratory rotations in three different participating groups working on both basic and translational stem cell biology.
  • Study fundamental aspects of Stem Cell Biology through a series of teaching modules led by leaders in the field.
  • Learn a variety of techniques, such as advanced imaging, flow cytometry, and management of complex data sets.

Students are expected to choose a laboratory for their thesis research by June 2019, and will then write a research proposal to be assessed for the MRes Degree in Stem Cell Biology. This assessment will also be used to determine whether students continue on to a 3-year PhD.

Physical Biology of Stem Cells
Incorporated into the ‘Stem Cell Biology’ Programme, opportunities are available specifically for candidates with a Physical, Computational or Mathematical Sciences background, wanting to apply their training to aspects of Stem Cell Biology *.

Great inroads have been made towards understanding how stem cells generate tissue and sustain cell turnover, most of which have been made by studying the biochemistry of stem cells. Less is known of their function across scales – from molecules to tissue – or interaction with their physical environment. We aim to identify the importance of physical, chemical, mathematical and engineering considerations in stem cell functionality. This could include mathematical modelling, engineering controlled environments to control stem cell function, single molecule approaches to study molecular interactions, systems biology, or investigating stem cell’s response to forces in its environment.

Eligibility
We welcome applications from those who hold (or expect to receive) a relevant degree.  You must have a passion for scientific research.

Stem Cell Biology and Medicine Programme (funding by the Wellcome Trust)

We welcome applications from EU and non-EU candidates. The Wellcome Trust provide full funding at the ‘Home/EU’ rate. Funding does not include overseas fees, so non-EU applicants will need to find alternative funding sources to cover these.

‘Physical Biology of Stem Cells’ Programme (funding by the Medical Research Council)

We welcome applications from UK/EU candidates, with a Physical Sciences, Mathematical or Computational Sciences background. *The Medical Research Council provide full funding for UK applicants only. Applicants from EU countries other than the UK, are generally eligible for a fees-only award. Please check your eligibility status at https://www.mrc.ac.uk/skills-careers/studentships/studentship-guidance/student-eligibility-requirements/ before applying.

Application Process
Visit https://www.stemcells.cam.ac.uk/study/ for full details, including how to apply.

Closing date: 4 January 2018
Interviews are likely to be held on: 30th January 2018 to 1st February 2018

Enquiries are also welcome via email to sci-phd@stemcells.cam.ac.uk.

The University values diversity and is committed to equality of opportunity.

The University has a responsibility to ensure that all employees are eligible to live and work in the UK.

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Funded PhD Positions – Purdue Center for Plant Biology

Posted by , on 7 November 2017

Closing Date: 15 March 2021

PURDUE UNIVERSITY CENTER FOR PLANT BIOLOGY

 

Purdue University is seeking graduate students to train for high-tech science careers in basic plant sciences through the Center for Plant Biology.

 

Purdue has invested more than $20 million in plant sciences and hired ten new faculty members since 2015 to expand research and education in basic plant biology. Graduate students in the Center for Plant Biology (CPB) have access to an innovative curricula, diverse research opportunities, and world-class facilities and resources.

 

WORLD-CLASS FACILITIES AND RESOURCES

State-of-the-art plant imaging technology and expertise to support basic research in a broad range of subdisciplines. >>Learn more

 

DIVERSE RESEARCH OPPORTUNITIES

This community of 35 faculty members provides a dynamic training environment for graduate students to study a breadth of research areas. >>Learn more

 

RESEARCH AREAS

  • Ecological and evolutionary genetics
  • Plant and insect chemical ecology
  • Reproductive cell biology
  • Cell wall biology
  • Cytoskeleton and membrane dynamics
  • Plant pathogen interactions
  • Hormone and stress physiology/biology
  • Plant metabolism
  • Biochemical genetics
  • Regulation of photosynthesis
  • Genetics, epigenetics and genomics
  • Computational biology

 

START YOUR PH.D.

Apply through the Purdue University Interdisciplinary Life Science Program (PULSe) by December 1 and specify Integrated Plant Sciences as your training group

>>Apply Now

 

FINANCIAL SUPPORT

All students admitted to our graduate program receive paid tuition and an assistantship for the first year, which allows students to complete core requirements and participate in laboratory rotations. Financial support for students in subsequent years comes from training grants, research grants secured by the major professor, or research and/or teaching assistantships. Given solid academic standing and lab performance, the level of support in subsequent years will meet or exceed the level of support provided in the students first year.

purdue.ag/cpb

FOR MORE INFORMATION
Clint Chapple, Director
cpb@purdue.edu

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Stem Cells Pave the Way for new treatment of diabetes

Posted by , on 7 November 2017

A new stem cell study conducted at the University of Copenhagen shows how we may increase the vital production of insulin in patients suffering from diabetes. The discovery helps to more efficiently at less cost make insulin-producing beta cells from human stem cells. Therefore, the research paves the way for more effective treatment of diabetes. The method may also prove significant to the treatment of a series of other diseases.

Stem Cells

415 million people worldwide have been diagnosed with diabetes. And the number continues to rise. Common to all diabetes patients is that they lack the ability to produce sufficient amounts of insulin, which regulates the blood sugar in the body. This can lead to a number of complications and in many cases be potentially fatal.

A new study conducted at the University of Copenhagen, which has just been published in the internationally acclaimed journal Nature Cell Biology, shows how researchers using human stem cells can produce insulin-producing cells that in the future can be transplanted into diabetes patients.

‘By identifying the signals that instruct mouse progenitor cells to become cells that make tubes and later insulin-producing beta cells, we can transfer this knowledge to human stem cells to more robustly make beta cells, says Professor and Head of Department Henrik Semb from the Novo Nordisk Foundation Center for Stem Cell Biology at the Faculty of Health and Medical Sciences.

The Cells’ Development Depends on their Sense of Direction
The research group, which in addition to Henrik Semb consists of Ph.D. Zarah Löf-Öhlin and assistant professor Pia Nyeng, among others, originally set out to study how the body creates the complex piping systems that transport fluids and gasses in our organs.

They wanted to understand the machinery for instructing progenitor cells into their different destinies. To their surprise, the mechanism turned out to be simple. According to Assistant Professor Pia Nyeng, these processes are mainly controlled by the progenitors’ ability to tell up from down (the cells’ so-called polarity).

Stem Cells

Hormone-producing cells (green and red) in the pancreas are formed in close contact with the piping system (blue)

‘It turns out that the same signal – the so-called epidermal growth factor (EGF) pathway – control both the formation of pipes and beta cells through polarity changes. Therefore, the development of pancreatic progenitor into beta cells depends on their orientation in the pipes. It is a really amazing and simple mechanism, and by affecting the progenitor cells’ so-called polarity we can control their conversion into beta cells’, says Pia Nyeng.

Exciting Potential for Diabetes Treatment
The study is mainly based on tests performed on mice, but the researchers decided to examine whether the same mechanism can be found in human cells.

’Zarah Löf-Öhlin discovered that the same cell maturation mechanism applies to the development of human cells. Now we can use this knowledge to more efficiently turn human stem cells into beta cells in the laboratory with the hope to use them to replace lost beta cells in patients suffering from diabetes’, says Henrik Semb.

The researchers expect regulation of cell polarity to be key to the development of many other human cell types, for example nerve cells. This may contribute to the development of stem cell therapy targeted at other diseases.

The article ‘EGFR signalling controls cellular fate and pancreatic organogenesis by regulating apicobasal polarity’ has been published in Nature Cell Biology.

Contact information

Professor Henrik Semb
Mail address: semb@sund.ku.dk
Telephone: +45 23 48 11 48

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Categories: Research

Musings of an accidental scientist

Posted by , on 6 November 2017

As we sat together at a farewell dinner after I graduated from Princeton University, my advisers asked me, “What got you into science?”. Although a simple, straightforward question on the surface, it sent me down memory lane and I found it incredibly difficult to provide a concise, one-line response.

I grew up in a rural settlement just outside the town of Udhampur which is situated in the Indian state of Jammu and Kashmir. A typical day involved school-time, helping my father and uncle at their grocery and stationary stores, playing street cricket, and planning activities around the daily power-cuts. Pursuing a bachelor’s degree was considered a distant dream and further education was unheard of in the area. Accordingly, I listened to the modest academic expectations from family and society, and ended up doing just well enough that no one ever complained. However, one fateful day in 6th grade forever changed this complacent attitude. During one of the lectures, the science teacher in the school called out one of the top students in the class who was siting besides me and also happened to be my close friend. She advised her, “Avoid the company of Yogesh. He is going to spoil you, and make you like him”. The teacher was correct in identifying me as neither academically sincere nor hard-working, and as I comprehended the truth in her words my face reddened with embarrassment. At the same time, I realized it as an opportunity for me to study hard and prove her wrong. Consequently, this had a substantial, even revolutionary, impact on me. For the first time I became serious about studying and generally succeeding academically. Fortunately, I found that I enjoyed studying and learning new scientific concepts. This was further reinforced by some exceptional teachers at school and family support at home. What began as a source of shame and embarrassment, slowly became point of pride! My interest in science continued to grow and I spent much of my teenage years solving interesting problems in physics and math.

Based on my performance in a certain exam during high school, I was assigned to major in chemical engineering for my undergraduate studies at IIT Gandhinagar in India. Here again, I experienced a crucial juncture in my sophomore year that made me realize how much I enjoyed research. Thanks to Prof. Narayanamurthy who taught us the first course in chemical engineering, I went from carefully planning a career pursuing an MBA after undergraduate studies to genuinely appreciating the nuances of chemical engineering. Importantly, I actively explored opportunities to be involved in research projects at my undergraduate institution. This, in turn, naturally led me to apply for PhD programs in chemical engineering.

I came to Princeton set on continuing my studies in chemical engineering; however, after taking a chemical reaction engineering course taught by my eventual adviser, Stanislav Shvartsman, I became intrigued by the chemistry inside living cells. He drew elegant parallels between reactions that happen in a chemical plant and in a living cell. This and subsequent interactions with another future adviser, Trudi Schüpbach, fostered a curiosity in biological questions. A lack of formal training in biology made the transition challenging, but it was also exciting to delve into a new field. Specifically, I was fascinated by how complex structures and functional forms emerge from elemental embryonic states. How are desirable properties such as precision, reproducibility, and robustness imparted to biological systems? Subsequently, my PhD focused on answering such fundamental developmental biology questions in the context of the early embryonic patterning in fruit flies (see here for details).

Together, fortuitous interventions bolstered by persistent hard work have led me to a place where I wake up every morning excited about going to lab and doing science. As I now embark on a foray into new biological research directions for my postdoctoral work, a diverse set of life and research experiences have taught me that nothing is impossible. Above all, one must follow their passion, work with inspiring and supportive mentors, and take risks.

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Research Assistant in Developmental and Regenerative Medicine – University of Oxford

Posted by , on 6 November 2017

Closing Date: 15 March 2021

Research Assistant in Developmental and Regenerative Medicine
Department of Physiology, Anatomy and Genetics & Weatherall Institute of Molecular Medicine, University of Oxford
Grade 6: £28,098 p.a.
Applications are invited for an experienced and meticulous Research Assistant to join the Cardiovascular Development, Repair and Regeneration team working under the direct supervision of Professor Paul Riley and Dr Filipa Simoes. The project is funded by the British Heart Foundation.

The aim of the project and team is to decipher the cellular and molecular mechanisms involved in the regenerating epicardium of the adult zebrafish heart. The Research Assistant will be responsible for carrying out a range of molecular and cell biological procedures, as well as assisting with experimental zebrafish work. Previous molecular biology and embryology experience is essential but relevant training in cardiovascular development and state of the art techniques will be provided where necessary. A range of different techniques will be used including CRISPR/Cas9 technology, Nanostring analysis, in situ hybridisation and multiplex hybridisation chain reaction, tissue cryosectioning, immunofluorescence microscopy, microinjection of zebrafish embryos, cell sorting, and management of wild type and genetically modified zebrafish lines. The post is ideally suited for a candidate with an interest in developing a career that involves working at the interface of Developmental Biology and Regenerative Medicine, with a strong background in the former.

This project is a collaboration between the Departments of Physiology Anatomy and Genetics, and the Weatherall Institute of Molecular Medicine.

Candidates must have a degree in a relevant field. Expertise in molecular biology techniques, histology, and imaging, with experience of animal models including husbandry and small animal surgery is preferable.

You will be based across two sites: the Sherrington Building, South Parks Road, Oxford, OX1 3PT and the Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DS.

The position is offered until 31 December 2018. An early start date is preferable.

The closing date for applications is 12.00 noon on Wednesday 29 November 2017. Interviews will be held on Thursday 14 December 2017.

Further details are available here:  https://www.recruit.ox.ac.uk/pls/hrisliverecruit/erq_jobspec_version_4.display_form

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