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Researchers in Frankfurt observe later root development cell by cell in a high-tech microscope
FRANKFURT. In contrast to animals, plants form new organs throughout their entire life, i.e. roots, branches, flowers and fruits. Researchers in Frankfurt wanted to know to what extent plants follow a pre-determined plan in the course of this process. In the renowned journal “Current Biology”, they describe the growth of secondary roots of thale cress (Arabidopsis thaliana). They have observed it cell by cell in a high-tech optical microscope and analysed it with computer simulations. Their conclusion: root shape is determined by a combination of genetic predisposition and the self-organization of cells.
“Our work shows the development of the complex organ of the secondary root with unprecedented temporal and spatial resolution”, says Professor Ernst H. K. Stelzer of the Buchmann Institute for Molecular Life Sciences at Goethe University Frankfurt am Main. He is the inventor of the high-resolution and gentle light sheet fluorescence microscopy, with which the researchers recorded the development of secondary roots from the first cell division to their emergence out of the main root. For over 64 hours, they first logged the fluorescence signals from cell nuclei and plasma membrane every five minutes and then identified and followed all cells involved in root development.
The secondary roots stem from a variable number of “founder cells”, of which some contribute to the development. The shape of the secondary roots and the respective growth curves show great similarities. “We classified the cell divisions on the basis of their spatial orientation in order to find out when new cell lines and cell layers form”, explains Daniel von Wangenheim, first author of the study. “Surprisingly, we were not able to predict on the basis of the initial spatial arrangement where exactly the future centre of the secondary root would lie.” Evidently, only the first division of the founder cells is strongly regulated, whilst the subsequent divisions do not follow any pre-determined pattern. Their behaviour is rather more adaptive. In nature, this also makes sense, for example if the roots meet with an obstacle.
In order to be able to identify the fundamental principles of secondary root development in the vast amount of data, the researchers combined methods for the quantitative analysis of cell divisions in wild and genetically modified plants (wild type and mutants) with mathematical modelling. This was undertaken by their colleague Prof. Alexis Maizel from the University of Heidelberg. He realized that the development of the secondary root is based on a limited number of rules, which account for the growth and orientation of cells. The development of a characteristic secondary root follows the principles of self-organization, which is prevalent in nature. Alexander Schmitz, co-author of the study, explains the non-deterministic part by the fact that organ development is robust as a result: “In this way, the roots are able to develop in a flexible and nevertheless controlled manner despite the varying arrangement of the cells and mechanical factors in the surrounding tissue.”
Publication: Daniel von Wangenheim, Jens Fangerau, Alexander Schmitz, Richard S. Smith, Heike Leitte, Ernst H.K. Stelzer, Alexis Maizel: Rules and self-organizing properties of post-embryonic plant organ cell division patterns, in: Current Biology, 28.1.2016, DOI: doi:10.1016/j.cub.2015.12.047
Online publication: http://dx.doi.org/10.1016/j.cub.2015.12.047
Video on YouTube: https://youtu.be/OffLqVUI8hE
Information: Prof. Dr. Ernst H. K. Stelzer, Alexander Schmitz, Buchmann Institute for Molecular Life Science, Goethe University, Phone +49(0)69 798-42547 or -42551, firstname.lastname@example.org email@example.com
Fluorescent protein markers delivered under high pressure
Tracing distinct proteins in cells is like looking for a needle in a haystack. In order to localize proteins and decipher their function in living cells, researchers label them with fluorescent molecules. However, the delivery of protein markers is often insufficient. A group of researchers from the Goethe University, working in close collaboration with US colleagues, has now found a solution for this problem. In the current issue of Nature Communications, they report on a process that uses pressure to deliver chemical probes in a fine-tuned manner into living cells.
"Although more and more protein labeling methods utilize synthetic fluorescent dyes, they often suffer from problems such as cell permeability or low labeling efficiency. Moreover, they cannot always be combined with other protein labeling techniques", explains Dr. Ralph Wieneke from the Institute of Biochemistry at the Goethe University.
Recently, the working group led by Wieneke and Prof. Robert Tampé developed a marker that localizes selected proteins in cells with nanometre precision. This highly specific lock-and-key element consists of the small synthetic molecule trisNTA and a genetically encoded His-tag.
In order to deliver this protein marker into cells, the researchers from Frankfurt, together with colleagues from the Massachusetts Institute of Technology (MIT), Cambridge, USA, applied a procedure in which a mixture of cells together with the marker were forced through narrow constrictions. This process is called cell squeezing. Under pressure, the cells incorporate the fluorescent probes with an efficiency rate greater than 80 percent. In addition, the process enabled to squeeze one million cells per second through the artificial capillary in high-throughput.
Since the marker binds very efficiently and specifically to the target protein and its concentration can be precisely regulated within the cell, the researchers were able to record high resolution microscopy images in living cells. Moreover, they were able to trace proteins with the marker only when activated by light. Thus, cellular processes can be observed with high precision in terms of space and time.
The researchers can even combine their labeling methods with other protein labeling techniques in living cells to observe several proteins simultaneously in real time. "Utilizing cell squeezing, we were able to deliver a number of fluorescently labeled trisNTAs in cells. This tremendously expands the scopes of conventional as well as high resolution microscopy in living cells", explains Prof. Robert Tampé. In future, it will be possible to follow dynamic processes in living cells in time and space at high resolution.
A picture is available for downloading here: www.uni-frankfurt.de/59861753
Caption: Utilizing the small lock-and-key element, the nuclear envelope protein Lamin A was stained with fluorescently labeled trisNTA (green). By orthogonal labeling methods, other proteins can be visualized simultaneously within the same cell (Histon 2B in magenta; Lysosomes in blue; Microtubuli in red).
Publication Alina Kollmannsperger, Armon Sharei, Anika Raulf, Mike Heilemann, Robert Langer, Klavs F. Jensen, Ralph Wieneke & Robert Tampé: Live-cell protein labelling with nanometre precision by cell squeezing, in: Nature Communications, 7:10372,
Information: Dr. Ralph Wieneke, Institute for Biochemistry, Riedberg Campus, Tel.: (069) 798-29477, firstname.lastname@example.org.
Alexander von Humboldt Foundation gives 250,000 Euro Prize for cooperation with LOEWE research center SAFE
Following a nomination by the Research Center SAFE, the Alexander von Humboldt Foundation has granted an Anneliese Maier Research Award 2016 to Marti G. Subrahmanyam, Charles E. Merrill Professor of Finance, Economics and International Business at the Stern School of Business, New York University. Purpose of the grant is the promotion of international cooperation in the humanities and social sciences. The award of 250,000 EUR will be used over a period of five years to finance research cooperation between Subrahmanyam and SAFE/Goethe University. The official host will be Loriana Pelizzon, SAFE Professor of Law and Finance.
Marti Subrahmanyam has published numerous articles and books in the area of corporate finance, capital markets and international finance. His current research interests are the valuation of corporate securities, options and futures markets, corporate debt markets, market microstructure and liquidity, and Indian financial markets. Subrahmanyam studied at the Indian Institute of Management and the Indian Institute of Technology Madras before he started his doctoral studies at the Massachusetts Institute of Technology (MIT) in Cambridge, USA, where he earned a Ph.D. in 1974.
Goethe University Frankfurt’s concept tested in six clinics/long-term effect confirmed
FRANKFURT. Social difficulties are one of the main problems for children and adolescents with Autism Spectrum Disorder (ASD). Especially when their intelligence is unaffected, they become more and more conscious in the course of their development of the fact that they are different. In the framework of group therapy developed at Goethe University Frankfurt, children and adolescents with high functioning ASD can learn how to cope better in the social world and also achieve a lasting effect. This is confirmed by clinical trials which examined 209 children and adolescents between the ages of 8 and 18 over the course of three years.
“We often encounter children and adolescents with Autism Spectrum Disorder in clinical practice who would like to communicate with youngsters of their own age and at the same time experience every day that they meet with rejection because they are unable to understand many of their classmates’ behaviour patterns. And this causes them to despair”, explains Professor Christine Freitag, Head of the Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy. Together with Dr. Hannah Cholemkery, she has developed a behavioural group therapy programme with instructions and exercises for the improvement of social skills.
To date, group therapies for the training of social skills for people with ASD have predominantly been investigated in the USA in the framework of smaller trials without any measurement of stability. The objective of the “SOSTA-net Trial”, led by Christine Freitag and coordinated by Hannah Cholemkery and in which six university hospitals in Germany participated, was to examine whether the social responsiveness of children and adolescents with ASD could be raised by means of group-based behavioural therapy. This took place with the aid of a standardized questionnaire (on the basis of a Social Responsiveness Scale – SRS), in which 65 behaviour patterns were evaluated by the parents before the start of group therapy, at the end of the intervention as well as three months after the end of the intervention in order to measure stability.
Therapy took place once a week over the course of three months in a group with four to five youngsters of the same age and two therapists. There were also three parent evenings. The results were compared with those of a wait list control group. There was a clear improvement in social behaviour in the intervention group, which also remained stable after three months when examined again.
In particular children with severe symptoms and a higher IQ at the beginning of the therapy were able to profit from it.
Christine Freitag, Hannah Cholemkery et al.: Group-based cognitive behavioural psychotherapy for children and adolescents with ASD: the randomized, multicentre, controlled SOSTA - net trial, in: Journal of Child Psychology and Psychiatry (2015), DOI: 10.1111/jcpp.12509
Further information: Professor Dr. Christine M. Freitag, Dr. Hannah Cholemkery, Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Tel.: (069) 6301-84055, Hannah.Cholemkery@kgu.de
Approval for Collaborative Research Centre (CRC) on selective autophagy led by Frankfurt scientists/Cooperation with the University Medical Center Mainz
FRANKFURT. The German Research Foundation (Deutsche Forschungsgemeinschaft/DFG) has approved 11 M € for the next four years for establishing a CRC on selective autophagy under the lead of Goethe University. Autophagy literally means "self-eating" and refers to a sophisticated system in which cellular waste is specifically detected and removed. It contributes to regular cell renewal, secures quality control and protects against diseases. Defects in this pathway can promote cancer development and neurodegenerative diseases like Parkinson, and contribute to infectious diseases and inflammatory reactions. The objective of the CRC is a better understanding of autophagy at the molecular and cellular level. In future, the researchers hope to be able to specifically target autophagy for improving the therapy of diverse diseases.
Professor Birgitta Wolff, President of the University, congratulated the researchers: “Well done to Ivan Dikic and his team for achieving this important milestone. The research planned within the CRC forms a promising basis for the development of new and more effective therapies. We are particularly pleased that we will be joining forces with Mainz University, the Institute of Molecular Biology in Mainz and the Georg-Speyer-Haus in the CRC – a further sign of the vitality of our regional partnerships.”
Autophagy is conserved from simple organisms such as yeast up to complex ones like humans. Typical targets for autophagy are harmful or superfluous proteins - it degrades for example aggregated proteins, which can otherwise lead to severe damage and cell death, as observed in numerous neurodegenerative diseases. Even entire cell organelles and invading pathogens such as bacteria or viruses can be eliminated via this pathway. The building blocks generated through this degradation process are recycled, which is why autophagy also functions as a survival strategy in times of low energy supply.
Autophagy is a highly complex and precisely regulated process which requires a concerted action by numerous players: The target substrate needs to be specifically recognized and surrounded by membranes to form what is known as the autophagosome. Autophagosomes fuse with lysosomes, which are cell organelles filled with digestive enzymes, finally enabling the breakdown of all cargo into the individual building blocks.
“The enormous significance of autophagy for the pathophysiology of diseases has only been recognized in the past decade. As a result, research activity in this field has increased rapidly”, explains Professor Ivan Dikic, CRC Speaker and Director of the Institute of Biochemistry II at Goethe University. “By strategic recruitments over the past five years, we have succeeded in developing Frankfurt into a centre for autophagy research. Now we are in a position to address many of the unanswered questions: What triggers autophagy? How does the cell select targets for autophagy? How does this pathway crosstalk to other cellular mechanisms and how is it involved in the pathogenesis of human diseases?”
Meanwhile it is known that the role of autophagy strongly depends on the cellular context: In healthy tissues, it prevents the emergence of cancer cells. At the same time, however, cancer cells capitalize on autophagy to overcome bottlenecks in nutrient supply, which occur as a result of rapid tumour growth. The researchers are now analysing this complex interaction. So far, little is known about the interplay of autophagy with other mechanisms, such as cellular trafficking (endocytosis), programmed cell death (apoptosis) and the ubiquitination system, which marks proteins for degradation in the proteasome.
Within the newly established CRC, researchers will study autophagy at the level of molecules, cells and model organisms. It is the first large-scale collaborative project in this field in Germany and allows scientists in Frankfurt and Mainz to position themselves in an internationally highly competitive field. A broad line-up of disciplines is needed to tackle the open questions, and therefore, within the CRC, structural biologists have teamed up with biochemists, cell biologists and clinicians. New insight into the molecular mechanisms underlying autophagy will be directly transferred to model systems for human diseases.
At Goethe University, the three faculties of Biological Sciences, Biochemistry, Chemistry and Pharmacy, and Medicine, and the cross-disciplinary Buchmann Institute for Molecular Life Sciences (BMLS) are participating in the CRC. Partners outside the University are the Institute for Pathobiochemistry at the University Medical Center of Johannes Gutenberg UniversityMainz (Prof. Dr. Christian Behl is Vice Speaker of the CRC), the Georg-Speyer-Haus in Frankfurt and the Institute of Molecular Biology gGmbH in Mainz.
Further information: Prof. Ivan Dikic, Institute of Biochemistry II, University Hospital Frankfurt, Tel.: (069) 6301-5652, Ivan.Dikic@biochem2.de.
Goethe University is a research-oriented university in the European financial centre Frankfurt founded in 1914 with purely private funds by liberally-oriented Frankfurt citizens. It is dedicated to research and education under the motto "Science for Society" and to this day continues to function as a "citizens’ university". Many of the early benefactors were Jewish. Over the past 100 years, Goethe University has done pioneering work in the social and sociological sciences, chemistry, quantum physics, brain research and labour law. It gained a unique level of autonomy on 1 January 2008 by returning to its historic roots as a privately funded university. Today, it is among the top ten in external funding and among the top three largest universities in Germany, with three clusters of excellence in medicine, life sciences and the humanities.
Publisher: The President of Goethe University
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