Goethe-Universit盲t 鈥� Press releases

看片软件 PR & Communication Department聽

Nov 12 2024

10:24

Newly discovered mechanism helps detach and recycle parts of cellular canal membranes as needed 鈥� models developed using supercomputer simulations

Bulges calculated in the supercomputer: How cells digest their internal canal system

Inside cells, there exists an extensive system of canals known as the endoplasmic reticulum (ER), which consists of membrane-encased tubes that are partially broken down as needed 鈥� for instance in case of a nutrient deficiency. As part of this process, bulges or protrusions form in the membrane, which then pinch off and are recycled by the cell. A study by 看片软件 Frankfurt has examined this protrusion process using computer simulations. Its finding: certain structural motifs of proteins in the ER membrane play a central role in this process. The study was carried out as part of the 鈥淪CALE - Subcellular Architecture of Life" cluster initiative.

FRANKFURT. The endoplasmic reticulum functions as a reservoir for calcium and carbohydrates and also serves as the site for the synthesis of various hormones. Cells adjust the expansion and networking of their internal canal system as needed. A process known as ER-phagy (鈥淓R-eating") plays a central role here. During this process, a part of the membrane of an ER tube bulges out and eventually pinches off into a small vesicle. At the same time, a kind of internal cellular 鈥渢rash bag", the autophagosome, forms around it. This then fuses with another container that contains highly reactive enzymes, which 鈥渟hred" the contents of the 鈥渢rash bag" and recycle it.

鈥淲e have known for several years that specific proteins, known as ER-phagy receptors, play a key role in this process," explains Dr. Ramachandra Bhaskara from 看片软件's Institute of Biochemistry II. These receptors are located in the membrane of ER tubes and consist of an anchor that inserts into the membrane. Attached to this anchor are two long protein strands that extend outward from the membrane surface like flexible tentacles. 鈥淯sing complex simulations in supercomputers, we were recently able to show, together with other research groups, that the anchor causes the membrane to curve," Bhaskara says, adding that 鈥渦nder certain conditions, this can result in a protrusion. In the current study, we have demonstrated that the filamentous structures increase the likelihood and significantly accelerate the formation of such a bulge."

Proteins form disordered 鈥渢entacles" from amino acids

Most proteins adopt a defined three-dimensional shape after they are produced: some parts form coiled, helical structures, while others fold back and forth like the bellows of an accordion. This gives them a compact, relatively rigid form, which also applies to the anchor region of ER-phagy receptors. The tentacles, however, consist of long chains of amino acids that oscillate back and forth in a largely disordered manner 鈥� which is also why they are referred to as 鈥渋ntrinsically disordered (protein) regions" or IDRs for short. These extensive movements require space, which they create by causing the membrane in which they are anchored to bulge. 鈥淎dded to this is another effect," emphasizes Dr. Sergio Alejandro Poveda Cuevas, the study's first author: 鈥淭he IDRs contain short sequences that can fold back under certain conditions. We were able to show that they do this during the formation of the bulges. They then nestle against the membrane like a scaffold, thereby reinforcing its curvature."

The pinching-off is thus the result of various finely orchestrated processes, as demonstrated by the simulation: initially, the anchor regions of various ER-phagy receptors approach each other. This clustering increases the curvature of the membrane caused by the receptors. Initially, the IDR tentacles are extended. They make contact with the autophagy machinery and direct it toward the membrane. The IDRs then condense into more compact structures, further enhancing the bulge until the membrane pinches off and the vesicle is packaged in the autophagosome (鈥渢rash bag").

Findings could prove important for the treatment of certain diseases

鈥淚n addition to offering a detailed insight into this important cellular process, our study also shows that receptor IDRs play a crucial role in ensuring smooth functioning," Bhaskara explains. These results are particularly interesting because some congenital neurological diseases are associated with disrupted ER-phagy. A better understanding of the membrane degradation process might one day enable targeted manipulation.

The study was funded by the German Research Foundation (DFG) within the framework of Collaborative Research Center 1177, and by the ENABLE cluster project funded by the Hessian Ministry of Science and Research, Arts and Culture.

Publication:
Sergio Alejandro Poveda-Cuevas, Kateryna Lohachova, Borna Markusic, Ivan Dikic, Gerhard Hummer, Ramachandra M. Bhaskara: Intrinsically disordered region amplifies membrane remodeling to augment selective ER-phagy. PNAS (2024)

Movie/Image for download:
Image sequence:
Movie (19 MB):

Caption (image and movie): The ER-phagy receptor FAM134B is initially distributed via the membrane surface (left). Its IDRs move back and forth in a largely disordered manner, like tentacles. The formation of local clusters initiates the curvature of the membrane (2nd from left), which is further strengthened by the condensation of the tentacles into more compact structures (2nd from right). The pinching off of the membrane vesicle (not shown) is initiated by a targeted redistribution of proteins (sorting, right). Image: Bhaskara Group, 看片软件 Frankfurt

Further information
Dr. Ramachandra M. Bhaskara
Head of 鈥淐omputational Cell Biology" working group
Institute of Biochemistry II
看片软件 Frankfurt
Tel.: +49 (0) 69 6303-2508
bhaskara@med.uni-frankfurt.de
Homepage:

Twitter/X: @goetheuni @IBC2_GU @RamBhaskara4 @HummerLab @DikicLab @EnableFrankfurt @sfb1177 @SCALE_Uni_FFM @MPIbp

Nov 6 2024

16:08

鈥淧oetics of Rhythm鈥�: German Research Foundation (DFG) funds Reinhart Koselleck Project by Professor Achim Geisenhansl眉ke聽

Rhythm as 鈥渇orm in motion鈥� and its significance for poetics

What is the significance of rhythm for poetics? Literary studies research has not yet answered this question exhaustively. Professor Achim Geisenhansl眉ke wants to change this. He will work on the poetics of rhythm within a Reinhart Koselleck Project funded by the German Research Foundation (DFG).

FRANKFURT. 鈥淧oetics of Rhythm" 鈥� that is the title of a project currently in the starting blocks at 看片软件 Frankfurt. The aim of Professor Achim Geisenhansl眉ke, Professor for Literary Theory and Comparative Literature, is to unfold the possibilities of a poetics of rhythm, which have not yet been fully exploited by literary studies, both systematically and historically. He combines the question of the fundamental significance of rhythm for the theory and practice of poetry (= poetics) with that of concrete manifestations of this phenomenon in poetry from modernity to the present day.

At the heart of the research work is rhythm in poetry. Is rhythm in poetry not simply meter? Not at all, says Achim Geisenhansl眉ke. Although rhythm also describes 鈥渇orm in motion" in poetic speech, it is far more encompassing than the concept of meter. Especially with regard to modern poetry, the potential offered by the concept of rhythm has so far hardly been studied. In his approach, Geisenhansl眉ke is above all continuing the work of Henri Meschonnic (1932-2009), the French poet, linguist and literary scholar who induced an upward revaluation of the concept of rhythm as part of a critical analysis of structuralist and post-structuralist literary theories.

Achim Geisenhansl眉ke's project will approach the topic in three sub-studies: The first will focus on rhythm in the poems of Friedrich H枚lderlin, the second will critically examine Foucault's theory of discourse and Meschonnic's theory of rhythm, while the third sub-study is dedicated to rhythm as 鈥渇orm in motion" in modern poetry up to the present day, from Annette von Droste-H眉lshoff and Charles Baudelaire to Thomas Kling.

The financial support from the German Research Foundation (DFG) allows the freedom needed to pursue all these aspects. The project will receive 鈧�750,000 in increments spread over five years, which can be distributed flexibly for teaching replacements, recruiting staff, assistants, workshops and conferences.

The funding line, which has existed since 2008, is named after Reinhart Koselleck (1923-2006), one of the most important German historians of the 20th century, who is considered a co-founder of modern social history. Reinhart Koselleck Projects are awarded to 鈥渙utstanding researchers with a proven scientific track record". The prerequisites for approval are exceptionally innovative approaches or a higher degree of risk.

In the case of Achim Geisenhansl眉ke's project, the risks lie in the attempt, within a comparative approach, to take rhythm, a concept that is as central to literary studies as it is underestimated, and use it to give poetics new impetus: No risk, no gain.

A portrait photograph of Professor Achim Geisenhansl眉ke is available for download at: https://www.puk.uni-frankfurt.de/160017255

Caption: Within a Reinhart Koselleck Project, Professor Achim Geisenhansl眉ke is examining the role of rhythm as a concept in literary theory. (Photo: Uwe Dettmar)

Further information
Professor Achim Geisenhansl眉ke
Department of Literary Theory and Comparative Literature
Faculty of Modern Languages
看片软件 Frankfurt
Tel. +49 (0) 69 798-32869
gei senhanslueke@lingua.uni-frankfurt.de

Nov 6 2024

15:28

International study led by 看片软件 Frankfurt sheds light on previously unknown interaction

New mechanism: How cancer cells escape the immune system

An international team led by 看片软件 Frankfurt has identified an intracellular sensor that monitors the quality of so-called MHC-I molecules, which help the immune system recognize and kill harmful cells, including tumor cells. The sensor ensures that defective MHC-I molecules remain inside the cell, where they are eventually degraded. Surprisingly, a lack of this quality assurance can lead to more MHC-I molecules reaching the surface of cancer cells, triggering a stronger immune response against the tumor.

FRANKFURT. It is comparatively easy to tell a cell's state of health: On their surface, cells present fragments of almost all the proteins they contain inside. This means the immune system can directly recognize whether a cell has been infected by a virus or has been dangerously altered by a mutation.

Countless molecular 鈥渞adio masts" 鈥� the MHC-I molecules 鈥� are responsible for presenting these fragments. They are assembled inside the cell and then transported to the membrane, the lipid layer surrounding the cell. Here, the masts are anchored such that the cargo faces outside and can be detected by troops of the immune system constantly patrolling the body. If these troops detect harmful molecules being presented on the MHC-I radio masts, they kill the relevant cell. A requirement, however, is that the masts themselves are fully functional; otherwise, there is a risk that this mechanism will not work and harmful cells escape the immune system. 鈥淲e have now discovered a sensor inside the cell that ensures that only functional MHC-I molecules are transported to the plasma membrane, while the defective units are eliminated," explains Dr. Lina Herhaus, who until recently conducted research on this topic at 看片软件's Institute of Biochemistry II and is now leading an independent research group at Braunschweig-based Helmholtz Centre for Infection Research.

Cells continuously produce a large number of proteins to sustain their manifold functions. If errors occur during this process, the affected molecules are usually eliminated. Specialized receptors recognize defective proteins and route them to mini garbage bags, where they are broken down. 鈥淎s part of our study, we searched for yet unknown receptors and came across a protein called IRGQ, which is specifically responsible for ensuring the quality control of the MHC-I radio masts," says Herhaus.

The researchers used genetic interference to suppress the production of IRGQ. The result: defective radio masts accumulated in the cells, some of which were also incorporated into the cell membrane, together with their functional counterparts. 鈥淵ou would actually expect cells without IRGQ to trigger a weaker immune response. However, this is obviously not the case: Having analyzed various human tumors, we found that less IRGQ was associated with a better survival rate of patients with liver cancer," explains Prof. Ivan 膼iki膰 from the Institute of Biochemistry II, who co-led the study with Herhaus. The patient data was also confirmed in an experimental liver cancer mouse model: In animals without IRGQ, the immune system attacked tumor cells much more aggressively; as a result, the rodents without IRGQ survived the cancer significantly longer.

IRGQ could represent a target structure for new drugs, at least for liver cell carcinomas 鈥� the world's second most deadly type of cancer. 鈥淲e have found a new mechanism by which tumor cells evade the immune system. In further studies, we will now examine IRGQ's influence on other types of cancer," emphasizes 膼iki膰. 鈥淥ur findings could be used in future to develop new therapies for liver cancer. One example would be to use drugs to target IRGQ for degradation and thereby stimulate the immune response against the cancer."

Irrespective of this, the newly discovered mechanism is also exciting for basic research. 鈥淲e want to find out how important IRGQ is for the functioning of the immune system in general, including during viral infections," says Herhaus. 鈥淭he results of our study raise a whole series of interesting questions, the answers to which can deepen our understanding of the body's immune defense."

Publication: Lina Herhaus, Ux铆a Gestal-Mato, Vinay V. Eapen, Igor Ma膷inkovi膰, Henry J. Bailey, Cristian Prieto-Garcia, Mohit Misra, Anne-Claire Jacomin, Aparna Viswanathan Ammanath, Ivan Bagari膰, Jolina Michaelis, Joshua Vollrath, Ramachandra M. Bhaskara, Georg B眉ndgen, Adriana Covarrubias-Pinto, Koraljka Husnjak, Jonathan Z枚ller, Ajami Gikandi, Sara Ribi膷i膰, Tobias Bopp, Gerbrand J. van der Heden van Noort, Julian D. Langer, Andreas Weigert, J. Wade Harper, Joseph D. Mancias, Ivan 脨iki膰: IRGQ-mediated autophagy in MHC-I quality control promotes tumor immune evasion. Cell (2024),

Participating institutions:
Institute of Biochemistry II, 看片软件 Frankfurt
Dana-Farber Cancer Institute, Harvard Institutes of Medicine
Department of Cell Biology, Harvard Medical School
Institute of Biochemistry I, Universit盲tsmedizin Frankfurt
Buchmann Institute for Molecular Life Sciences, 看片软件 Frankfurt
Max Planck Institute of Biophysics, Frankfurt
University Medical Center, Johannes Gutenberg University Mainz
Department of Cell and Chemical Biology, Leiden University Medical Center

Images for download:

Captions:
1. Cells: Once cells' quality control mechanism is activated, IRGQ (red) accumulates in special cell organelles, the lsysosomes (green). This is also where the degradation of the non-functional MHC-I molecules takes place. Photo: Dr. Lina Herhaus, 看片软件 Frankfurt
2. IRGQ-Structure (pink/orange) IRGQ is anchored via another protein (gray) in the membrane of the 鈥済arbage bags" in which the non-functional MHC-I molecules are packaged. The bags later fuse with the lysosomes, which initiates the degradation of the molecules. Image: Henry Bailey, 看片软件 Frankfurt

Further information
Professor Ivan 脨iki膰
Institute of Biochemistry II
and Buchmann Institute for Molecular Life Sciences
看片软件 Frankfurt
Tel: +49 (0) 69 6301-5964
dikic@biochem2.uni-frankfurt.de

Lina Herhaus, Ph.D.
Group Leader - Immune Signaling
HZI - Helmholtz-Zentrum f眉r Infektionsforschung GmbH
Lina.herhaus@helmholtz-hzi.de

Twitter/X: @goetheuni @IBC2 @Helmholtz_HZI

Nov 4 2024

10:32

看片软件 adopts paper on the tension between academic freedom, freedom of expression and social responsibility

Science between freedom and responsibility

On the occasion of its 110th anniversary, 看片软件 Frankfurt released a paper outlining its positioning in the area of tension between science鈥檚 social responsibility, academic freedom and freedom of opinion. Its main message: the university offers science a space for autonomy and creativity while simultaneously defending it against non-scientific interests. However, this autonomy also has its limits and requires responsible handling, both on the part of the university as well as its members and affiliates. The paper supplements the university's mission statement and specifies the rights and obligations both of the university and its academics, as derived from Germany鈥檚 Basic Law and other legal norms.

FRANKFURT. The paper reaffirms 看片软件鈥檚 self-image as a place where different academic views meet and struggle to make available groundbreaking knowledge. 鈥淪cience thrives on dialog, discussion and discourse with stakeholders both inside and outside of academia. This is especially true for our university, which was founded by Frankfurt鈥檚 urban society for its urban society. In such a culture, academics have to withstand the possibility that others may publicly contradict them or protest against their academic events 鈥� as long as such criticism or process remains within the confines of the law. That being said, whenever academic freedom is threatened by statements or actions, it falls upon us as a university to protect it,鈥� explains 看片软件 President Prof. Enrico Schleiff. 鈥淚t is important to remember that academic freedom does not apply to every statement made or event organized by scientists: There are indeed cases where they express their private opinions, for example on fields for which they are no experts, or pursue purely results-oriented ideological goals with an event. Such instances fall outside the domain of academic freedom and therefore outside the university's sphere of influence.鈥�

The paper was developed to provide a better basis for dealing with public criticism of and protests against public events organized by 看片软件 academics. 鈥淢any debates are highly polarized. If we want to pursue science in dialog with society, we must neither shy away from nor avoid it,鈥� explains Schleiff. 鈥淎s professors, we are trained for scientific discourse. But we also have to learn how to deal with criticism and arguments that are not of a scientific nature and how to remain confident in emotionally heated situations.鈥� That is why the university has set up new training courses, including in facilitation and communication, to strengthen scientists鈥� skills, also during confrontational moments.

The paper was drawn up by an expert commission headed by legal scholar Prof. Matthias Jahn. In legal terms, it has the character of an administrative regulation that specifies standards: By explaining the applicable law, it serves as a binding guideline for all university members. It cannot, however, account for every individual decision. 鈥淭he university makes its infrastructure available to its researchers so they can pursue science, not to carry out on-scientific activities and formats. Determining whether or not this is the case requires a case-by-case consideration, which also accounts for the standards of the respective subject culture,鈥� Jahn explains. 鈥淭he university鈥檚 management is not permitted to control the content of science, and controversies about the way in which knowledge is gained and interpreted fall under the scientific community鈥檚 responsibility. However, the university management can decide, for example, not to make rooms available for an event that is not subject to academic freedom if this decision is organizationally safeguarded in such a manner that a structural threat to academic freedom can be excluded. If academics consider such a decision to be wrong, they have recourse to the courts.鈥� The courts, in turn, have to consider the specifics of the university's self-conception, explains Jahn, who has worked at various higher regional courts on a part-time basis for two decades.

The paper also clarifies that although academic freedom is guaranteed extensively in Germany鈥檚 Basic Law, this is no blank check guarantee for limitless scientific practice: It is possible to impose restrictions in individual cases in favor of goods that are considered to have greater merit, such as fundamental and human rights, freedom of education for students or the personal rights of third parties. If this is the case, the consequences can be severe: 鈥淰iolations of this obligation (...) can constitute misconduct鈥�, the paper states.

The administrative regulation specifying the standard was adopted by 看片软件鈥檚 Executive Board following earlier debates in both the Senate and the University Council. The draft was also discussed with representatives of Frankfurt municipality.

The official wording of the new administrative regulation:

Nov 4 2024

07:58

Plans for joint research and teaching cooperation / Concert marks 看片软件鈥檚 110th anniversary

看片软件 and Jewish Academy sign cooperation agreement

看片软件 Frankfurt and the Jewish Academy operated by the Central Council of Jews in Germany [Zentralrat der Juden in Deutschland] are planning to deepen their cooperation. The relevant cooperation agreement was signed on October 30, 2024, by Central Council President Dr. Josef Schuster and 看片软件 President Prof. Enrico Schleiff. The signing ceremony was followed by a reception and concert in the hr broadcasting hall, celebrating 看片软件鈥檚 110th birthday.

FRANKFURT. The Jewish Academy is currently being set up in Frankfurt. Once operational, it will become an important center for the study of Jewish history and religion, culture and intellectual thought and both take up and enrich current debates 鈥� whether with regard to research, academic teaching or interaction with society. With this in mind, 看片软件 and the Jewish Academy have entered into an 鈥渋nstitutional cooperation in the sense of a permanent and consistent academic collaboration鈥�, as outlined in the contract signed last Wednesday. Headquartered in Frankfurt, the Jewish Academy considers itself 鈥渁n intellectual hub and center of attraction for Jews from Germany and Europe, members of other religious communities and interested members of the public who are curious about Jewish, intercultural, interreligious or universalist issues.鈥�

鈥淭his cooperation builds on our university鈥檚 rich historical tradition as well as numerous present-day collaborations,鈥� explained President Schleiff. 鈥淎s an institution established by Frankfurt citizens for both urban and wider society, we owe our existence in large part to the city鈥檚 Jewish citizens of the time, who were among the founders of the endowed university in 1914. In the early 1920s, Franz Rosenzweig founded the Freie J眉dische Lehrhaus [Free Jewish Teaching House], which had many touch points with Frankfurt University. To this date we maintain a strong focus on Jewish religious studies, philosophy and Jewish studies, complemented by topics that extend beyond the boundaries of religion, including the dynamics of religion, cultures of remembrance or 'education after Auschwitz', to name just a few examples. Both this and the previous semester, we held a lecture series titled 'Antisemitism. Culture of Remembrance. Democracy鈥�, together with the Central Council's education academy, the Jewish Academy鈥檚 predecessor 鈥� also with a view towards the historical amnesia that has unfortunately manifested itself since Hamas鈥� October 7 attack on Israel.鈥�

鈥淭his cooperation is greatly important for the Jewish Academy and for Jewish life, not just in Frankfurt, but throughout Germany,鈥� says Central Council President Dr. Josef Schuster. 鈥淚t is here where common academic interests are lived, deepened and expanded. There already exist several projects that can now be cast in this new form. Universities are key to a modern society鈥檚 central nervous system, and their malfunctioning could plunge us all into the abyss. Ever since October 7, 2023, many German universities have become a setting for the darkest aspects of our society. It is partnerships like this that give us confidence that these forces will not prevail. By entering into this cooperation with the Jewish Academy, 看片软件 Frankfurt is taking an important step together with Jewish life, thought and perspectives on our society in these turbulent times.鈥�

鈥淎s a foundation university established on the initiative of many Jewish citizens, 看片软件 Frankfurt has stood for equal opportunities and the integration of Jewish perspectives in academia and society for more than a century,鈥� Hessian Minister President Boris Rhein said. 鈥淭his cooperation with the Jewish Academy not only builds on and continues this tradition, it also deepens it in a special way and carries it into the future. In times like these, it is particularly important to truly live cultural and religious diversity and to strengthen our society鈥檚 democratic resilience by means of institutional cooperation.鈥�

鈥淭his cooperation creates a very special bond between 看片软件 Frankfurt, which owes its foundation largely to the efforts of large Jewish families, and the Jewish Academy run by the Central Council umbrella organization, which at the same time serves as the representative of Germany鈥檚 Jewish communities,鈥� added Uwe Becker, Hessen鈥檚 state commissioner for Jewish life and the fight against antisemitism and a state secretary in the Hessian Ministry of Finance, who conveyed minister Rhein鈥檚 greetings at the signing ceremony. 鈥淚t combines the tradition of the Jewish Teaching House with the underlying idea that teaching and learning be linked and anchored in society. I am certain that this will result in a think tank for Jewish and non-Jewish perspectives on our society鈥檚 development that is unique in Europe.鈥�

The strategic goals and fields of action outlined in the agreement signed in Frankfurt include the continuation of existing as well as the initiation of further research collaborations to address new research questions and perspectives from a transdisciplinary perspective and to enrich discourse. In addition, the cooperation seeks to strengthen collaborative research and cooperation with a focus on top international research, the joint acquisition of funds, as well as mutual support in the acquisition of partners. Beyond that, it sets the stage for research-oriented teaching, jointly supervised doctoral theses, the opening of selected events and joint lecture series, workshops, seminars or conferences as well as publications, among others.

Prof. Mirjam Wenzel, Director of the Jewish Museum Frankfurt and honorary professor at 看片软件 Frankfurt, also gave a keynote speech at the signing ceremony held on the premises of Hessischer Rundfunk (hr). Following the signing, 看片软件 celebrated its 110th birthday in the hr broadcasting hall with a reception and a concert by the symphony orchestra of Tel Aviv University鈥檚 Buchmann-Mehta School of Music under the direction of renowned conductor Zubin Mehta, featuring works by Ludwig van Beethoven and Paul Ben-Haim. In addition to those present at the signing ceremony, other guests included Federal Minister of Education Bettina Stark-Watzinger and Dr. Ina Hartwig, Head of Frankfurt鈥檚 Department of Culture and Science. Tel Aviv University has been a partner of 看片软件 Frankfurt since 1984. This special friendship was initiated by the joint Josef Buchmann Doctoral Scholarship Fund. The concert was a birthday present presented to 看片软件 by honorary senator Dr. h.c. Josef Buchmann and Dr. h.c. Bareket Buchmann.

看片软件

Press releases 鈥� November 2024