The International Max Planck Research School for Translational Psychiatry (IMPRS-TP) is offering PhD positions in molecular, cellular and systemic psychiatric research. Students are exposed to a wide range of scientific questions and methods covering areas of molecular medicine, neuroscience, psychiatry, quantitative epigenetics and imaging, neuroimaging, design-based stereology and clinical studies.

Research in a translational setting 

In addition to the traditional doctorate positions, trainee medical doctors are given the opportunity to be enrolled on an integrated PhD/residence program in psychiatry. Highlighting the translational facet, doctorate students will receive insights into clinical aspects of disease and trainee medical doctors will gain PhD level research expertise, while also developing their clinical skills.

Receive exceptional training for a successful career in research, clinic and academia! 

Structured curriculum: Core Course | Lecture Series | Methods Workshops | Soft Skills

Topics addressed range from molecular and cellular neuroscience, behavioral assessments, electrophysiology and brain imaging to psychological and clinical measures and outcomes, as well as, epidemiology, statistics and bioinformatics.

Work in an environment of scientific excellence and interdisciplinary collaboration 

IMPRS-TP is a joint initiative of leading scientists from the Max Planck Institutes of Psychiatry and of Neurobiology and the Ludwig Maximilians University, Munich. Further collaborations have been established with the Munich Medical Research School (MMRS), the Helmholtz Center Munich, the Graduate School of Systemic Neurosciences (GSN), Martinsried, Germany and King’s College London, UK. IMPRS-TP is co-funded by the Else-Kröner-Fresenius Foundation.

Call for applications 

IMPRS-TP welcomes applications from doctoral candidates coming from any country who hold a 4 year Bachelor or Master of Science (or an equivalent degree) in a relevant field or a Medical Degree. Applications from trainee medical doctors with laboratory experience are particularly encouraged. IMPRS-TP will only accept applications submitted through the IMPRS-TP online application tool. Applications submitted by mail or email will not be considered. Application deadline is January 2nd, 2018.

For more information, visit http://www.imprs-tp.mpg.de/ 

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The Great Wall of Collagen IV
During the long history of evolution, the key innovation that gave rise to animals with true tissues was the extracellular matrix, very conserved from sponges to humans [1]. Before I started my PhD in the lab of Jose C. Pastor-Pareja at Tsinghua University in Beijing, he had described how the matrix protein Collagen IV is secreted and deposited into the matrix basement membranes (BMs) of the Drosophila fruit fly larva for shaping tissues and organs [2]. This research attracted my attention since I felt I’d like to understand the process and functional significance of extracellular matrices in building tissues. In my mind, extracellular matrices such as the BM were like the Great Wall (Figure 1), shaping, delimiting and defining tissues while keeping them from invasive damage.

Basement membranes are specialized planar matrices underlying epithelial and endothelial tissues, and surrounding nerves, muscles and adipocytes [3,4]. Collagen IV, thought to be an exclusive BM component, is a heterotrimer made of three alpha chains. These trimers can interact with each other to form a higher order scaffold. Despite a lot of research into extracellular matrices and a great deal of biochemical characterization, there are still many mysteries for developmental and cell biologists to solve. For instance, the hierarchy of assembly of BM components in vivo, why basement membranes are continuous planar layers rather than more amorphous structures or how matrices maintain the diverse organization of tissues and impact their physiology. In both flies and humans, adipose cells, called fat body cells in Drosophila,n IV, tissue morphog are cells of mesodermal origin lacking epithelial structure and yet they form true compact tissues. Our recent paper published in Current Biology shows how Collagen IV-containing structures different from BMs hold adipocytes together.

How it all started

One of the most wonderful tools we have in flies is protein traps, allowing visualization of endogenous proteins tagged with GFP. With the help of a Collagen IV functional GFP trap, we are able to visualize BMs very easily at great resolution. Collagen IV is widely regarded as an exclusive component of the planar BMs, not present in other more disordered types of matrices. However, images of the fat body, a favorite subject of study in our lab, always showed intercellular accumulations of Collagen IV that did not look as thin or continuous as BMs (Figure 2). We decided to call these novel structures CIVICs, which is short for Collagen IV Intercellular Concentrations. We then confirmed through electron microscopy that CIVICs were discontinuous, irregularly shaped and much thicker than BMs, for instance the one surrounding the fat body itself. Jose is a big fan of electron microscopy and always encourages us to include it in our projects. This is despite the fact that electron microscopy is a challenging and time-consuming technique, especially with fat body cells, which are difficult to handle because they are full of lipid droplets.

Adhesion and signaling by CIVICs

Finding these novel Collagen IV structures that looked so different from a BM in wild type flies was very exciting. The important question, though, was whether they were an accident, like fibrotic aggregates our lab had previously found [5], or they had an actual role. Knock down of Collagen IV created gaps between adipocytes in the normally continuous tissue layer, indicating that CIVICs were gluing cells together (Figure 3). At that point, we realized we had something truly interesting in our hands. Soon afterwards, we had the data showing that integrins and syndecan, another extracellular matrix receptor, were involved in the formation of CIVICs and in holding adipocytes together. This we highly anticipated, at least for integrins. However, it was a bit surprising to see that other BM components localized to CIVICs but did not have the same kind of effects as Collagen IV, especially for Laminin, which most people would place first in the hierarchy of assembly of the BM polymer. This is definitely an issue for further research for us.

So far, we had the evidence showing CIVICs contributed to intercellular adhesion and therefore maintenance of tissue organization. The final question to address clearly was the functional consequences of this organization. Something we had noticed in our experiments knocking down Collagen IV, integrins or Syndecan was that the fat body cells did not become as large as the wild type. They did not seem to be undergoing anoikis or other kind of apoptosis, but they did not look entirely happy to us. Because others in the lab were working on vesicle trafficking in these cells, we had the tools for checking lysosome and autophagosome formation. Indeed, we saw that eliminating CIVICs triggered autophagy in these cells, which is something they normally will do if unhappy, for instance under conditions of starvation. Further experiments led us to connect CIVICs to the known PI3K/Akt anti-autophagy pathway through Src, explaining how CIVICs prevented these cells from undergoing autophagy (Figure 4). In summary, these peculiar Collagen IV intercellular structures were important for both maintenance of adipose tissue structure and physiology.

Reviewer concerns:

We appreciated that reviewers gave us many useful suggestions about quantifying our results and conducting appropriate statistical analysis. It was a lot of work, but we have to agree the paper is now more rigorous. Among other referees, concerns, the most difficult item to do was immune staining for electron microscopy, to prove that the structures we were characterizing actually contained Collagen IV. Since fat body cells are full of lipid droplets, they are very easy to break during the multiple fixation, permeabilization, staining and dehydration steps. I failed many times with immuno-gold staining. Others in the lab have been using APEX fusions for EM localization with amazingly good results, but there wasn’t enough time for us to create a Collagen IV-APEX transgenic line. Just at the moment I almost want to give up, I got the images with clear staining using HRP-coupled secondary antibodies and DAB reaction (Figure 5).

Final thoughts

We think our work opens new doors in the extracellular matrix and BM field, showing that the Collagen IV=BM equivalence may not be as strict as previously thought. It actually adds to work by others showing that Collagen IV-containing structures may not be all flat and homogeneously thin, blurring distinctions between BMs and more amorphous matrices [6,7]. We would definitely love to know whether structures similar to CIVICs can be seen in other Drosophila tissues or in mammals. Another distinction that is blurred by our work is that between adhesion proteins and matrix, as one could argue that Collagen IV at CIVICs is working as an intercellular adhesion molecule [8].

Finally, it is worth pointing out that the Great Wall and other defensive walls in history were, unlike The Wall in Game of Thrones, discontinuous systems of smaller walls. Actually, and despite their intended purpose, they were quite porous and ended up facilitating contacts between the peoples on both sides, enhancing commerce and cultural exchanges across them. In that sense, the Great Wall metaphor for how a system of CIVICs maintains adipocytes connected may still work.

This post is a comment on the paper: Dai, J., Ma, Mengqi., Feng, Zhi, and Pastor-Pareja, José (2017). Inter-adipocyte Adhesion and Signaling by Collagen IV Intercellular Concentrations in Drosophila. Current Biology. 18, 2729-2740.

References

1.  Hynes, R.O., and Naba, A. (2012). Overview of the matrisome-an inventory of extracellular matrix constituents and functions. Cold Spring Harb. Perspect. Biol. 4, a004903.
2.  Pastor-Pareja, J.C., and Xu, T. (2011). Shaping cells and organs in Drosophila by opposing roles of fat body-secreted Collagen IV and Perlecan. Dev. Cell 21, 245–256.
3.  Yurchenco, P.D. (2011). Basement membranes: cell scaffoldings and signaling platforms. Cold Spring Harb. Perspect. Biol. 3, a004911.
4.  Jayadev, R, and Sherwood, D.R. (2017) Morphogenesis: Shaping Tissues through Extracellular Force Gradients. Curr. Biol. 17, 850-852.
5.  Zang, Y., Wan, M., Liu, M., Ke, H., Ma, S., Liu, L.P., Ni, J.Q., Pastor-Pareja, J.C. (2015). Plasma membrane overgrowth causes fibrotic collagen accumulation and immune activation in Drosophila adipocytes. eLife 10.7554/eLife.07187.
6.  Medioni, C., and Noselli, S. (2005). Dynamics of the basement membrane in invasive epithelial clusters in Drosophila. Development 132, 3069-3077
7.  Isabella, A.J., and Horne-Badovinac, S. (2016). Rab10-Mediated Secretion Synergizes with Tissue Movement to Build a Polarized Basement Membrane Architecture for Organ Morphogenesis. Dev. Cell 38, 47-60.
8.  Zajac, A.L., Horne-Badovinac, S. (2017). Tissue Structure: A CIVICs Lesson for Adipocytes. Curr Biol. 27(18)1013-1015.

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The Graduate School Life Science Munich (LSM) offers an international doctoral programme to motivated and academically qualified next generation researchers at one of Europe’s top Universities. With over 40 research groups from the Faculty of Biology and the Faculty of Chemistry and Pharmacy of Ludwig Maximilian University (LMU) München, the LSM in its prominent location within the HighTechCampus in Martinsried south of Munich, contributes to the enormous possibilities for support, interdisciplinarity and constant scientific input from the surrounding laboratories. LSM members are internationally recognized for their innovative research approaches and technologies, they are aiming to answer essential questions relevant to basic and applied biological and biochemical research. Within their own research group or in collaboration with a specialized research group on campus, LSM doctorates are given many opportunities to learn and command a variety of techniques. Furthermore, the graduate programme holds various workshops and seminars that strengthen and prepare doctorates for a successful career as scientists, as well as for non-academic routes. All courses, lectures and seminars at the LSM are held in English. Thus, selected candidates have to be fluent in both written and spoken English.
Successful students of the graduate school will be awarded a doctoral degree (Dr. rer. nat.) by the LMU after 3 to 4 years. Candidates need to prove a strong qualitative background as well as interest and ability to conduct independent research.

The doctoral programme is open for students who hold either a master´s or diploma degree, as well as to exceptional candidates with a four years bachelor degree (with written thesis).

LSM calls for doctoral candidates! Available research projects cover areas from Biochemistry, Cell and Developmental Biology, Climate Change, Ecology, Evolutionary Biology, Genetics, Microbiology, Pharmacology, and Plant Sciences. Applicants are selected in a multi-step process through our online portal, currently open until November 29th, 2017, thus ensuring openness and fairness throughout the application procedure. Every complete submission is processed and evaluated by the LSM coordinator. These are then independently reviewed by several faculty members of the LSM Graduate School. Based on academic qualification, research experience, motivation, scientific background and the letters of recommendation, candidates will be selected to participate in the LSM Interview week. After thorough evaluation through the LSM committee members, successful candidates will be invited to join the LSM Graduate School.

Further information and details about the online application process and the available research projects can be found here: http://www.lsm.bio.lmu.de/application/index.html

View link for poster: 2170612_LSM_Plakat_A3_2017_lay5

Contact information:

Graduate School Life Science Munich

Francisca Rosa Mende

Ludwig-Maximilians-University Munich

Faculty of Biology

Grosshadernerstr.

82152 Planegg-Martinsried

Germany

Tel: +49 (0) 89 / 2180-74765

E-Mail: info.lsm@bio.lmu.de

Website: http://www.lsm.bio.lmu.de

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Dear Colleagues,

I am PhD graduate in Biotechnology focusing on Insect Molecular Biology and Plant Virology. After completion of my PhD in Agriculture sector, I would like to switch my career to medical sciences or advance biotech tools like studies in stem cells, or CRISPR.

Should I repeat PhD in medical sciences or is there a possibility to get job or postdoc in the health sector with the same qualification?

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postdoc ad

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Our research seeks to investigate the fundamental question of how cardiac cells sense and respond to their environment. Focusing on tissue interactions we seek to understand the mechanisms underlying the regulation of morphogenic 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, but are not restricted to: how multiple tissues interact to regulate large movements? How intercellular adhesions are tuned during collective movements? How lumen formation is intrinsically and extrinsically encoded? and How the plasticity of cardiovascular identity is regulated? These challenging questions require we take an interdisciplinary approach, combining the genetic and imaging strengths of zebrafish with both biomechanics and systems-level methodologies.

Are these the type of difficult challenges that excite you? We are recruiting graduate students to join our laboratory. Contact Josh directly at josh@olemiss.edu.

-More information about the laboratory can also be found at joshuabloomekatz.wordpress.com.

-Additional positions are 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

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Applications are invited from highly motivated and enthusiastic individuals for an MRC funded PhD position in the laboratory of Dr. Raman Das at the Faculty of Biology, Medicine and Health at the University of Manchester. This position will commence in September 2018.

The successful candidate will have or expect to obtain a first or upper-second class degree (or equivalent) in the biological sciences and will additionally have a strong interest in cell and developmental biology and in vivo imaging.

This exciting project builds on our recent discovery of a new form of cell sub-division (apical abscission) that regulates shedding of the apical tips of newborn neurons, leading to an acute loss of cell polarity and retention of the centrosome (Das and Storey, Science, 2014). How these neurons re-establish their polarity and subsequently extend an axon in the correct orientation is now a key question in the field. This project will focus on the role of the retained centrosome in re-establishment of polarity in the new-born neuron using a highly interdisciplinary approach integrating pioneering cell and developmental biology techniques. The successful candidate will utilise cutting-edge live-tissue imaging techniques to visualise centrosomal dynamics and microtubule architecture rearrangements during neuronal differentiation in the embryonic spinal cord. This approach will be complemented by super-resolution microscopy to visualise the fine sub-cellular architecture of differentiating neurons.

Overall this project lies at the critical interface between cell and developmental biology and is therefore likely to provide physiologically relevant insights into the molecular mechanisms leading to neuron polarisation and axon extension.

Further details and information on how to apply are available here

Further information about the University of Manchester MRC DTP programme is available here

Deadline for applications: 17th of November 2017

Applications from EU citizens are welcome

Informal enquiries are encouraged and should be directed to Dr. Raman Das at raman.das@manchester.ac.uk.

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I remember when I first started grad school.

I was pumped about my project, examining the signaling and physiological role of a novel dopamine receptor complex. We had experienced research associates, state-of-the-art equipment, and bold hypotheses. I was ready to take the first step on the road of biomedical discoveries. Then I faced my first obstacle:

Which antibody should I use for my Western Blot?

It’s one of those things that nobody really teaches you. My lab had well established protocols for many antibody-based applications, ranging from Western Blot, to immunofluorescence, to FRET, but we never had an established “protocol” for finding the most suitable antibodies. Yet, antibodies can often be the main determining factor for successful and reproducible experiments.

In this article, I’d like to outline a 10-step “protocol” as a guide for every antibody search. (Hint: it’s more than just Googling.)

1. Identify target antigen and alternative gene names

Use GeneNames to find out the approved nomenclature for the protein in study, as different proteins may share a common name. Then, use GeneCards to identify aliases to expand the possible search queries, as antibody suppliers may name the same protein using different aliases.

2. Define antigen restrictions

Decide the intended specificity for isoforms, functional domains, processed forms, domains with different subcellular localization (extracellular vs. intracellular etc.) and post-translational modifications of the protein in study.

3. Obtain canonical protein sequence

Use Uniprot to find out the amino acid sequence for the protein (and its isoforms) in study.

4. Determine potential cross-reactivity with other species or proteins

Analyze the sequence using NCBI’s BLAST tool to define whether there are distinct regions of the chosen protein containing linear epitopes that are unique to the individual antigen, as well as regions of the target antigen where antibodies are likely to cross-react with other proteins with which they share sequence identity.

5. Define the ideal epitope(s)

Depending on the study interest, the ideal epitopes could be unique regions in the target antigen conferring specificity or those conferring cross reactivity.

6. Decide applications

Antibodies are often more suitable for specific applications depending on whether they bind to linear (Western Blot and paraffin-embedded immunohistochemistry) or native (immunoprecipitation, frozen-section immunohistochemitry, flow cytometry, and ELISA) epitopes.

In addition, an antibody that recognizes a formalin-resistant epitope for immunohistochemistry may also work in another technique using formalin fixation, such as ChIP.

7. Decide primary antibody isotype and host

When probing with multiple primary antibodies in a single experiment, it may be advantageous to choose antibodies of distinct hosts or isotypes, allowing for detection of multiple targets using isotype- or host-specific secondary reagents conjugated with different fluorescent labels.

Examples include co-localization or protein-interaction studies.

8. Decide clonality of antibody

The clonality of the antibody should be determined based on the intended applications.

Polyclonal antibodies are produced by immunizing host animals with the antigen, and each batch contains a mixture of antibodies targeting various epitopes on the same antigen. As a result, polyclonals can enhance detection signals by enabling more antibodies to bind the same antigen to form large precipitating lattices. However, this lack of specificity limits the use of polyclonals to mainly Western Blot, which allows off target bindings to be distinguished as bands at various molecular weights.

On the other hand, since monoclonal antibodies are identical clones produced from a single hybridoma (uniquely identified by clone ID), they target a single epitope and a single isotype, thereby conferring higher specificity than polyclonals. Monoclonals are ideal for applications using native tissues, such as IP and flow cytometry.

9. Identify antibodies from the literature

Once the desired antigen and antibody characteristics have been defined, conduct extensive literature searches to identify antibodies that have been published in similar experimental contexts of interest (ie. same application, tissue, or cell line).

There are many resources that can help save time on the literature search, including BenchSci.

Review publications and carefully scrutinize antibody usage data. Watch out for antibodies that show discrepancies across the literature, such as an antibody detecting proteins of different molecular weights or showing different protein expression patterns in the same tissue type. If validation data were not presented in the paper, contact the authors to request this information.

10. Prioritize and validate antibody candidates

Generate a list of commercially available antibodies following the literature search. Prioritize the antibodies based on product data sheet to match the antigen and antibody characteristics defined in Step 1-8.

Keep in mind to always perform validation experiments (using knock-out, IP-MS, or CRISPR) prior to applying the antibody in your study.

What are the steps you usually took when searching antibodies? Let me know in the comment section below if I missed anything and I’ll update the “protocol” accordingly.

And to help you specifically with Step 9, why not register a free account on BenchSci to save time looking back and forth between vendor sites and papers?

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Postdoctoral Fellowship in the Center for Stem Cell and Organoid Medicine (CuSTOM)

A multidisciplinary team in the laboratory of Dr. Aaron Zorn is seeking to recruit a highly-motivated postdoctoral fellow to spearhead research investigating the molecular and cellular basis of trachea-esophageal birth defects using animal models and human organoids. The goal is to understand how the trachea and esophagus arise from the embryonic foregut during fetal development and to model how genetic mutations in patients can disrupt this process leading to life threatening congenital birth defects.

The Zorn lab (www.cincinnatichildrens.org/zorn-lab) is part of the new Center for Stem Cell and Organoid Medicine (www.cincinnatichildrens.org/custom) and the Division of Developmental Biology at Cincinnati Children’s Hospital, one of the top pediatric research institutions in the world. Qualified applicants will have a PhD with peer-review research publications, a demonstrated expertise in cell biology, morphogenesis or biomechanics, and a keen interest to establish an independent research program in development and stem cell biology.

Contact: Aaron Zorn, PhD aaron.zorn@cchmc.org

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The Fribourg Graduate School of Life Sciences (FGLS) is an interdisciplinary, international graduate school, which offers a coordinated doctoral program in life sciences at the University of Fribourg, Switzerland. It addresses doctoral students in the fields of biology, biochemistry, molecular medicine, chemistry, physics, bioinformatics, and mathematics who have a life science focus. State-of-the-art theoretical and experimental research will lead to a PhD in science.

Currently, we are recruiting students in the fields of:

• Molecular and Behavioral Neurogenetics | Sprecher Lab
• Plant Symbioses | Reinhardt Lab
• Chronobiology | Albrecht Lab
• Regenerative Biology in Zebrafish | Jazwinska Lab
• Protein Homeostasis/Regulation of Autophagy | Dengjel Lab
• Computational Biophysics and Biochemistry | Vanni Lab
• Chordate regeneration | Blanchoud Lab
• Eukaryotic Ribosome Biogenesis | Kressler Lab

We offer an integrated research and training program which leads to a PhD after three to four years. The entire program is run in English. It includes supervision and mentoring, as well as courses on novel technologies and soft skills. We expect applicants to have an excellent university degree and to be motivated and interested in interdisciplinary research subjects. Excellent communication skills in English are of benefit.

Candidates are requested to send by email a SINGLE PDF application including a CV, a brief statement of their research interests and the preferred lab, a copy of their Master diploma (with grades), and names of three referees to

Mrs Adeline Guélat
Department of Biology
adeline.guelat@unifr.ch

Application is open until October 31st, 2017. Interviews will take place in November/December 2017.

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