Synthetic vesicles are mini-laboratories for customised molecules
Cells of higher organisms use cell organelles to separate metabolic processes from each other. This is how cell respiration takes place in the mitochondria, the cell's power plants. They can be compared to sealed laboratory rooms in the large factory of the cell. A research team at Goethe University has now succeeded in creating artificial cell organelles and using them for their own devised biochemical reactions.
have been attempting to “reprogram" natural cell organelles for other processes
for some time – with mixed results, since the “laboratory equipment" is
specialised on the function of organelles. Dr Joanna Tripp, early career
researcher at the Institute for Molecular Biosciences has now developed a new
method to produce artificial organelles in living yeast cells (ACS Synthetic
To this end, she used the ramified system of tubes and bubbles in the endoplasmic reticulum (ER) that surrounds the nucleus. Cells continually tie off bubbles, or vesicles, from this membrane system in order to transport substances to the cell membrane. In plants, these vesicles may also be used for the storage of proteins in seeds. These storage proteins are equipped with an “address label" – the Zera sequence – which guides them to the ER and which ensures that storage proteins are “packaged" there in the vesicle. Joanna Tripp has now used the “address label" Zera to produce targeted vesicles in yeast cells and introduce several enzymes of a biochemical metabolic pathway.
This represents a milestone from a biotechnical perspective. Yeast cells, the “pets" of synthetic biology not only produce numerous useful natural substances, but can also be genetically changed to produce industrially interesting molecules on a grand scale, such as biofuels or anti-malaria medicine.
In addition to the desired products, however, undesirable by-products or toxic intermediates often occur as well. Furthermore, the product can be lost due to leaks in the cell, or reactions can be too slow. Synthetic cell organelles offer remedies, with only the desired enzymes (with “address labels") encountering each other, so that they work together more effectively without disrupting the rest of the cell, or being disrupted themselves.
“We used the Zera sequence to introduce a three-stage, synthetic metabolic pathway into vesicles," Joanna Tripp explains. “We have thus created a reaction space containing exactly what we want. We were able to demonstrate that the metabolic pathway in the vesicles functions in isolation to the rest of the cell."
The biotechnologist selected an industrially relevant molecule for this process: muconic acid, which is further processed industrially to adipic acid. This is an intermediate for nylon and other synthetic materials. Muconic acid is currently won from raw oil. A future large-scale production using yeast cells would be significantly more environment-friendly and sustainable. Although a portion of the intermediate protocatechuic acid is lost because the vesicle membrane is porous, Joanna Tripp views this as a solvable problem.
Professor Eckhard Boles, Head of the Department of Physiology and Genetics of Lower Eukaryotes observes: “This is a revolutionary new method of synthetic biology. With the novel artificial organelles, we now have the option of generating various processes in the cell anew, or to optimise them." The method is not limited to yeast cells, but can be utilised for eukaryotic cells in general. It can also be applied to other issues, e.g. for reactions that have previously not been able to take place in living cells because they may require enzymes that would disrupt the cell metabolic process.
Mara Reifenrath, Mislav Oreb, Eckhard
Boles, Joanna Tripp: Artificial
ER-Derived Vesicles as Synthetic Organelles for in Vivo Compartmentalization of
Biochemical Pathways, in:
ACS Synthetic Biology: https://doi.org/10.1021/acssynbio.0c00241
Dr. Joanna Tripp
Institute for Molecular Biosciences
Goethe University Frankfurt
Tel.: + 49 69 798 29516
Neanderthals introduced solid food in their children’s diet at around 5-6 months of age
Neanderthals behaved not so differently from us in raising their children, whose pace of growth was similar to Homo sapiens. Thanks to the combination of geochemical and histological analyses of three Neanderthal milk teeth, researchers were able to determine their pace of growth and the weaning onset time. These teeth belonged to three different Neanderthal children who have lived between 70,000 and 45,000 years ago in a small area of northeastern Italy.
FRANKFURT/KENT/BOLOGNA/FERRARA. Teeth grow and register information in form of growth lines, akin to tree rings, that can be read through histological techniques. Combining such information with chemical data obtained with a laser-mass spectrometer, in particular strontium concentrations, the scientists were able to show that these Neanderthals introduced solid food in their children's diet at around 5-6 months of age.
Not cultural but physiological
Alessia Nava (University of Kent, UK), co-first author of the work, says: “The beginning of weaning relates to physiology rather than to cultural factors. In modern humans, in fact, the first introduction of solid food occurs at around 6 months of age when the child needs a more energetic food supply, and it is shared by very different cultures and societies. Now, we know that also Neanderthals started to wean their children when modern humans do".
“In particular, compared to other primates" says Federico Lugli (University of Bologna), co-first author of the work “it is highly conceivable that the high energy demand of the growing human brain triggers the early introduction of solid foods in child diet".
Neanderthals are our closest cousins within the human evolutionary tree. However, their pace of growth and early life metabolic constraints are still highly debated within the scientific literature.
Stefano Benazzi (University of Bologna), co-senior author, says: “This work's results imply similar energy demands during early infancy and a close pace of growth between Homo sapiens and Neanderthals. Taken together, these factors possibly suggest that Neanderthal newborns were of similar weight to modern human neonates, pointing to a likely similar gestational history and early-life ontogeny, and potentially shorter inter-birth interval".
Home, sweet home
Other than their early diet and growth, scientists also collected data on the regional mobility of these Neanderthals using time-resolved strontium isotope analyses.
“They were less mobile than previously suggested by other scholars" says Wolfgang Müller (Goethe University Frankfurt), co-senior author “the strontium isotope signature registered in their teeth indicates in fact that they have spent most of the time close to their home: this reflects a very modern mental template and a likely thoughtful use of local resources".
“Despite the general cooling during the period of interest, Northeastern Italy has almost always been a place rich in food, ecological variability and caves, ultimately explaining survival of Neanderthals in this region till about 45,000 years ago" says Marco Peresani (University of Ferrara), co-senior author and responsible for findings from archaeological excavations at sites of De Nadale and Fumane.
This research adds a new piece in the puzzling pictures of Neanderthal, a human species so close to us but still so enigmatic. Specifically, researchers exclude that the Neanderthal small population size, derived in earlier genetic analyses, was driven by differences in weaning age, and that other biocultural factors led to their demise. This will be further investigated within the framework of the ERC project SUCCESS ('The Earliest Migration of Homo sapiens in Southern Europe - Understanding the biocultural processes that define our uniqueness'), led by Stefano Benazzi at University of Bologna.Publication: Alessia Nava, Federico Lugli, Matteo Romandini, Federica Badino, David Evans, Angela H. Helbling, Gregorio Oxilia, Simona Arrighi, Eugenio Bortolini, Davide Delpiano, Rossella Duches, Carla Figus, Alessandra Livraghi, Giulia Marciani, Sara Silvestrini, Anna Cipriani, Tommaso Giovanardi, Roberta Pini, Claudio Tuniz, Federico Bernardini, Irene Dori, Alfredo Coppa, Emanuela Cristiani, Christopher Dean, Luca Bondioli, Marco Peresani, Wolfgang Müller, Stefano Benazzi, Early life of Neanderthals. Proceedings of the National Academy of Sciences Oct 2020, DOI: 10.1073/pnas.2011765117
1. Fumane Cave near Verona (Wikipedia): This is where several of the milk teeth of Neanderthal children investigated by Professor Wolfgang Müller at Goethe University were found. https://de.wikipedia.org/wiki/Grotta_di_Fumane#/media/Datei:Grotta_di_Fumane_3.jpg
Neanderthal milk teeth: Presumably a Neanderthal child lost this
tooth 40,000 to 70,000 year ago when his or her permanent teeth came in.
Credit: ERC project SUCCESS, University of Bologna, Italy
Ultra-thin cut: Researchers at Goethe University cut
paper-thin slices off of a Neanderthal milk tooth. The teeth are subsequently
put back together and reconstructed. Credit/video still: Luca Bondioli and
Alessia Nava, Rome, Italy
Institute for Geosciences /
Frankfurt Isotope and Element Research Center (FIERCE)
Tel. +49 (0)69 798 40291,
Film and media scholars at Goethe University Frankfurt dissect the new media world of the pandemic
With the onset of the current pandemic, our lives have become more digital and more mediatized than ever before. But how can we understand this transformation, and how can we envision our lives in this “new“ media world? A new publication edited by a group of media scholars working in Frankfurt offers a glimpse of some of the research questions and challenges to come.
current pandemic poses a particular challenge for film and media scholars.
COVID-19 changes not just their work routines but transforms their very object
of study: the media. “As a consequence of the pandemic, we have to adapt
ourselves to new conditions of producing, accessing, consuming, sharing, and
deploying media for the flow of information, labor, goods, policies, and culture”,
says Laliv Melamed, post-doc researcher in the Graduate Research Training
Program “Konfigurationen des Films” (www.konfigurationen-des-films.de). Together with her colleague Phillipp
Keidl, Melamed has initiated and co-edited the collection “Pandemic Media”,
which appears as an open access publication this week.
“‘Pandemic Media‘ is an attempt to meet the challenges of the pandemic with a series of flashlight essays which address current and future research questions in media studies”, says professor Vinzenz Hediger, project director of “Konfigurationen des Films”. In that spirit, the publication’s subtitles is “Preliminary Notes Towards an Inventory”.
“Pandemic Media“ brings together 37 contributions from the scientific network of “Konfiguration des Films” – a network that is truly global. Contributors include researchers working at universities in New York, Stanford, Toronto, Seattle, Oxford, London, Lagos, Utrecht, Frankfurt, Weimar or Paris. The diversity of the contributors is reflected in the variety of their topics and perspectives: These include the now ubiquitous drone images, the split-screen aesthetics of video conferencing software, dating apps, Trump’s television strategy against COVID, visualisations of the virus or the development and implementation of the COVID tracing app in Germany.
The publication’s cover is based on the current work of MAGNUM photographer Antoine D’Agata, who has been documenting the impact of the pandemic in Paris streets and hospitals with a heat sensor camera. D’Agata’s eerily suggestive images, which are on display at the Brownstone Foundation in Paris until the end of October, are also the subject of one the contributions to the volume.
Among “Pandemic Media”‘s innovations is the digital open access publication strategy, which allowed the editors to put the project in the short space of four months. All contributions underwent a two-step double blind peer review process. The project director of “Konfigurationen des Films“ and Professor Antonio Somaini, who teaches at Université Paris-3 and is also a partner of Goethe University in the International Master Cinema Studies (IMACS, www.imacsite.net) serve as co-editors.
The publication date for the 37 contributions and the introduction is 28 October 2020. “Pandemic Media“ is the latest volume in the „Configurations of film“ series published by meson press. The full publication can be accessed here: https://meson.press/books/pandemic-media/, first in html format, later as PDF files for download. The publication will be available in book form in time for the holidays.
Meson press is an innovative new publisher specializing in open access publications on digital media culture. “From our point of view, ‘Pandemic Media’ is an exciting pilot project”, comments Andreas Kirchner, co-founder and co-director of meson press. “Not only does the volume perfectly fit our profile, it offers us an opportunity to experiment with groundbreaking new publication formats.”
The Graduate Research Training Program “Konfigurationen des Films“, which is funded by the Deutsche Forschungsgemeinschaft (DFG), has been studying the digital transformation of film culture since 2017. This summer, the second cohort of 12 doctoral candidates has assumed their positions and started their research projects.
Publication: „Pandemic Media. Preliminary Notes Towards an Inventory“, published by Vinzenz Hediger, Philipp Keidl, Laliv Melamed und Antonio Somaini
Images to download: http://www.uni-frankfurt.de/93471401
Caption: The temperature of the pandemic: The book cover is based on a photo by Magnum photographer Antoine D’Agata, who has been documenting Parisian street scenes and processes in hospitals with a heat-sensitive camera since April (Foto: Cover (c) meson press/Mathias Bär/Antoine D’Agata)
Graduate Research Training Program „Konfigurationen des Films“
Graduate Research Training Program „Konfigurationen des Films“
Prof. Dr. Vinzenz
Speaker of the Graduate Research Training Program „Konfigurationen des Films“
Physicists from Frankfurt, Hamburg and Berlin track the propagation of light in a molecule
Three-year German-American project studies biology of LRRK2
FRANKFURT. About ten percent of Parkinson's cases can be ascribed to mutations in the LRRK2 gene. Five research teams from the University of California in San Diego, Goethe University Frankfurt and the University of Konstanz want to explain in the next few years how mutations in the LRRK2 gene trigger Parkinson's disease and what possible targets there are for drugs. The US-American initiative “Aligning Science Across Parkinson's" has made the equivalent of € 6.1 million available for this project.
In the early 2000s, it was discovered that in many Parkinson's patients a certain enzyme called LRRK2 mutates and evidently plays a significant role in five to ten percent of hereditary Morbus Parkinson and between one and five percent of the spontaneous form. LRRK2 is an enzyme that attaches phosphate groups to other proteins in the human cell and is far more active than normal in the brain cells of Parkinson's patients, leading it to block transport processes in the cell. Many inhibitors against the LRRK2 enzyme have already been tested in the past, but they are not sufficiently effective or their side-effects are too severe.
The five teams from USA and Germany want now to elucidate in detail the enzyme's structure and how it works in the cell and thus create a basis for the targeted production of inhibitors. A first three-dimensional structure of the LRRK2 protein was recently published by the research team in the journal Nature. The initiative “Aligning Science Across Parkinson's", which is backed by The Michael J. Fox Foundation for Parkinson's Research, is supporting the project financially.
Co-Project Manager Stefan Knapp, Professor for Pharmaceutical Chemistry at Goethe University, explains: “By comparing LRRK2 mutations in Parkinson's patients with normal LRRK2, we want to find out which tasks LRRK2 assumes in the cell, how the enzyme moves three-dimensionally, and how the mutated LRRK2 contributes to nerve cells dying off. While the expertise of our colleagues in the USA lies in various imaging methods, here in Frankfurt we'll develop chemical probes to localize and study LRRK2 in cells and we will produce recombinant LRRK2 variants that will help us to understand their three-dimensional structure."
Co-Project Manager Florian Stengel, Professor for Cellular Proteostasis at the University of Konstanz, says: “In the framework of this project, we here in Konstanz want to identify the cellular interaction partners of LRRK2. In this way, we'll be able to complete our picture of its cellular role and thus make it possible to develop a drug against LRRK2 mutated Morbus Parkinson."
Article on the first three-dimensional structure of the LKKR2 protein: C K Deniston, J Salogiannis, S Mathea, D M Snead, I Lahiri, M Matyszewski, O Donosa, R Watanabe, J Böhning, A K Shiau, S Knapp, E Villa, S L Reck-Peterson, A E Leschziner. Structure of LRRK2 in Parkinson's disease and model for microtubule interaction. Nature. 2020 Aug 19 https://pubmed.ncbi.nlm.nih.gov/32814344/
Pictures to download: www.uni-frankfurt.de/92946466
Caption: Professor Stefan Knapp, Institute of Pharmaceutical Chemistry, Goethe University, Frankfurt (Foto: Uwe Dettmar)
Professor Stefan Knapp
Institute of Pharmaceutical Chemistry
Goethe University Frankfurt
Phone: +49 69 798-29871
Department of Biology / Laboratory of Cellular Proteostasis and Mass Spectrometry
University of Konstanz
Phone: +49 7531 88-5172