transCampus Projekte in 2024

Sex specific medicine is just a recent but nonetheless important scientific approach to adequately face “traditional” medical treatments that had been developed for a male-normed body without taking into consideration the sex-related differences in the functioning of male and female bodies.

Sexual dimorphism is an important factor for incidence and survival of cancer in non-reproductive organs, such as the adrenal gland. The research group previously demonstrated that pheochromocytomas (PCC) being neural crest-derived cell tumours (paraganglioma) of the adrenal medulla (the innermost part of the adrenal gland),  are more prevalent in females compared to males. Nevertheless, metastases in these chromaffin cell tumours are more common in males, but the mechanisms behind these sex differences are largely unknown and effective treatment strategies for aggressive diseases are still lacking.

The present project therefore aims to address the hypothesis that sex-specific differences in differentiation within the chromaffin cell lineage may contribute to the development of PGL and have implications for potential therapeutic approaches. Therefore, isogenic human induced pluripotent stem cells (hiPSCs) allowing for investigating differences between sexes will be used (see additional information below). In order to investigate at which step of differentiation from neural crest cells to chromaffin cells differences between sexes occur, a differentiation protocol for hiPSCs will be established starting with the work published by Abu-Bonsrah et al. In order to be able to realize the project within the time frame, the differentiation protocol will be established at the UKD and KCL in order to be able to test various approaches in parallel for the optimal conditions. Initially, the protocol will be established in one hiPSC and the success of the protocol will be validated by gene expression analysis (qRT-PCR and Western blot analysis). Subsequently, the protocol will be applied to both complementary hiPSCs and RNAseq will be performed at each differentiation step to obtain information about differences between sexes. After obtaining chromaffin-like cells, catecholamine content will be measured (HPLC-ECD) to prove functionality and single nuclei (sn)-RNAseq will be performed to obtain information about the heterogeneity and the transcriptional profile of the expected cell populations. These data will be correlated with sn-RNAseq data from PGL tissues and normal chromaffin cells (already available through a collaboration with Heidelberg) to identify potential mechanisms that explain the sex-dependent presentation of PGLs.

Furthermore, the project group aims to identify targets for a potential sex-specific therapy. The described model will be the first tool that allows for investigation of sex-specific differences in treatment response. Subsequently, chromaffin-like cells will be treated with different targeted drugs alone or in combination and treatment response will be assessed (viability assay).

The pooling of expertise of Achim Temme’s group at TU Dresden and Gilbert Fruhwirth’s group at King’s College London in this new transCampus collaboration contributes to a deeper knowledge for cancer immunotherapy and underlines the partner institutions shared focus on medical research.

Background: Cancer immunotherapy, in particular novel treatment modalities, has revolutionized medicine [Couzin-Frankel J, Science 2013]. One encouraging strategy is based on chimeric antigen receptors (CARs) for redirecting immune effector cells (T cells, NK cells) towards surface-exposed tumour-associated antigens (TAAs) [Cartellieri M et al., J. Biomed Biotechnol 2010]. The interaction of CAR-modified immune effector cells with TAAs on tumour cells at the immunological synapse has been considered to influence the fitness and survival of those cells. Importantly, ligation of CARs to TAAs is both mandatory for inducing tumour cell killing (by targeted secretion of granules loaded with cytotoxic proteins such as perforin and granzyme B) and can lead to cell membrane transfer from targeted tumour cells to CAR-modified immune effector cells, a process termed trogocytosis.

So far, the impact of CAR:TAA affinity on trogocytosis and downstream CAR-modified immune effector fitness, exhaustion, and survival remains elusive. Furthermore, identification of transferred membranes containing potential immunomodulators and signaling molecules may aid development of new approaches to improve adjuvant CAR-NK therapies.

This interdisciplinary TransCampus project builds on the multi-scale imaging expertise of the Fruhwirth group (King’s College London (KCL)) and the NK/CAR-NK immunotherapy expertise of the Temme group (TU Dresden (TUD)). The main objective of this project will investigate the impact of trogocytosis on CAR-NK cell therapy. Secondly, the project will focus on bystander trogocytosis of other surface proteins, such as receptor tyrosine kinases (RTK) and immune checkpoint ligands, which can affect CAR-NK activation/exhaustion statuses.

Expected results: The planned read-out systems are currently the most sensitive available and will be exploited to provide deeper insight into CAR:TAA-mediated trogocytosis. The research team expects to reveal, for the first time, the extent of bystander molecule transfer by trogocytosis and aims at identifying the immunomodulatory effects of these transferred molecules on CAR-NK/NK cell fitness and survival.

This new collaboration addresses the different levels and underlying mechanisms of demonisation of minorities, especially the LGBT community, in digital spaces and shows the breadth of disciplines of transCampus as it is the second one in humanities and social sciences.

This project develops an analytical framework through which to understand the processes by which minorities are demonised in political and media discourse. The demonisation of minorities – such as queer and trans people, migrants and refugees, or disabled people – plays a key role in public discourse where it often works to drive and legitimise political projects of democratic backsliding, the undermining of rights, and the erosion of social welfare systems (Castro Varela and Mecheril, 2016; Tyler, 2022). In the digital age, this process of demonisation has gained increased power through new media technologies, post-truth politics, and the spread of conspiracy theories (Reddi, Kuo & Kreiss, 2021; Banaji and Bhat 2021; Fuchs 2022).

This project analyses how the demonisation of minorities operates in digital discourse through a focus on LGBT rights, in particular, those of trans people who have become the subject of heated and often hostile media discourse over the last few years (Hark and Villa 2015; Patternote and Kuhar 2017; Peirce, Erikainen and Vincent 2020). It will examine how trans and gender nonconforming people have been represented in digital media spheres in Germany and the UK over the last decade. As a case study, this project will look at how political suggestions to change self-identification laws in both countries have led to often hostile and demonising debates that have little to do with the actual legal changes proposed, the existing research on the issue, or the concerns and questions around self-identification that need to be addressed. Instead, these discourses tend to operate as part of a wider stigmatisation and demonisation of trans and other LGBT subjects that drive right-wing nationalist politics and democratic backsliding in Europe and across the globe.

Through this case study, the project will develop a wider framework for how processes of demonisation operate in digital media by focusing on three levels:

• Digital architectures and networks – which digital networks do these forms of demonisation operate through?
• Political ideologies and discourses – what political discourses and networks are created and reproduced in this process?
• Affect and emotion – what affects and emotions drive processes of digital demonisation?

Through this analysis, the project will not only shed light on the ways in which LGBT discourses are key to animating anti-democratic politics across different national contexts today but also provide a wider framework for understanding the demonisation of minorities in digital culture today. The project will set the groundwork for a lasting collaboration on digital demonisation between TU Dresden and KCL that will result in a publication, a collaborative media lab, and a joint grant proposal.

This research collaboration focuses on multiple myeloma, the most frequent tumour in bones and bone marrow, and the mechanisms behind its resistance to current immunotherapy approaches.

The treatment landscape for patient with multiple myeloma has been revolutionised by the introduction of immunotherapy, most impressively by the advent of chimeric-antigen receptor T cells (CART) targeting B cell maturation antigen (BCMA) - Idecel and Ciltacel. Despite the impressive initial response rate of almost 90%, a considerable proportion of patients relapse within the first 12 months after treatment and have a poor prognosis. Whereas target antigen loss has been described as one reason for relapse after CART therapy in B-cell lymphoma and acute lymphoblastic leukaemia, this mode of resistance seems to be infrequent in multiple myeloma. Newer research points to tumour intrinsic factors being able to turn down the anti-myeloma immune response over time. In a systematic screen, the team of Dr. Benjamin has identified potential molecules and pathways which may help predict the response or resistance of individual patients.

In this collaborative project the participating researchers aim to undertake a comprehensive analysis of tumour intrinsic and tumour microenvironmental factors that mediate resistance to anti-BCMA CART cells by performing single cell RNA seq and CyTOF analysis of primary bone marrow (BM) and blood samples collected from relapsed myeloma patients pre and post Idecel or Ciltacel treatment applying established methods at KCL. A pilot study will be carried out with samples from up to 10 relapsed myeloma patients treated with Idecel or Ciltacel at Dresden. Single cell RNA seq of CD138 selected myeloma cells from BM will be performed and bioinformatics analysis used to identify genes that correlate with depth and duration of remission achieved with CART therapy and with relapse. Separately deep immune profiling of peripheral blood by CyTOF will be performed to investigate any correlation between specific immune cell subsets and response to CART therapy.

Partial funding

The excellent medical research resources and expertise of TU Dresden and King’s College London are brought together in this new collaboration that aims to further develop cancer diagnostics through photoacoustic imaging.

Photoacoustic microscopy is an emerging imaging method based local heating due to light absorption in tissue. It has the potential to enable label free cancer diagnosis given sufficient spatial resolution is achieved. To realise deep tissue diagnostics with minimal invasive keyhole access, in this project, the collaborating researchers will develop a miniaturised sub-millimeter fibre-optic endomicroscopy probe based on optical excitation of ultrasound with sub-micrometer resolution. Raster scanning is employed for spatially selective excitation. The system will be combined with sensitive acoustic detectors, which will enable to map spatial optical absorbance of the specimen. The optical sub-system will be setup and tested at TUD. The acoustical sub-system will be setup and tested at KCL. Validation will take place in London. The research group plans to establish a long-term cooperation with internationalisation of research and education. The leverage of the research towards biomedical applications in the clinic is pursued.

Until now the researchers in this project have conducted joint online lecturing within the scope of the advanced seminar on computational laser metrology at TU Dresden. The research group aims to extend the cooperation in lecturing for instance by introducing the partners research expertise in regular courses. For instance, the lecture on "Biomedical Laser Systems and Optogenetics" will benefit from introducing photo-acoustic imaging.

Emerged from a small-scale project with first contacts in 2023 the researchers in this collaboration contribute to a sustainable and socially just traffic transformation by addressing the behaviour of users of micromobility vehicles in cities.

This interdisciplinary inter-university project focusses on users of micromobility vehicles (e.g., e-scooters) - why they use the vehicles they use, and how they use them on the road. Different forms of micromobility hold the potential to contribute to a transition away from motorised vehicles towards more sustainable forms of transport, while also constituting a welcome addition to the mobility options, especially in urban areas. Indeed, despite being a comparatively recent phenomenon, micromobility vehicles enjoy an immense popularity in the cities in which they are available. However, as a result, their potential impact on road safety has been questioned, as injury crashes and violations of road rules are reported with increasing frequency. This project aims to make a small contribution to the growing body of research in this field, by focussing on the perceptions and behaviour of users of these vehicles.

In particular, the project group plans to mirror data collection activities that have been (or will be) carried out by TUD in Germany (e.g., surveys or on road observations) on the behaviour of users of micromobility vehicles in the UK. The garnered knowledge will be explored in subsequent research/bids to understand the impact of

• both the built in and natural environments
• the availability of mobility infrastructure
• cultural, social, and economical factors

To facilitate this, a joint workshop and research visits are planned to support the data collection effort, the subsequent data analysis, dissemination of the results to the scientific community, general public, and stakeholders, as well the scientific exploitation of the results for future project proposals.

At the same time, the workshop and visits will serve as tools for interdisciplinary exchange between the two research groups, to foster a better understanding for the methods and approaches of the respective partner's domain of expertise and research. The inclusion of early career researchers in the workshop and / or visits will be a vital element in this endeavour. It will help create the leaders of cross-disciplinary fields where mobility solutions are human centred and environment driven. The KCL investigators are part of the Net-Zero Centre and the Centre for Urban Science and Progress; thus, the workshops will benefit from the extended international network of these centres.

Partial funding

This new collaboration is part of the IRTG 2251 network “Immunological and Cellular Strategies in Metabolic Disease” and thus addresses, with its research subject, the biochemical processes of metabolic and cardiovascular diseases.

Mitochondria are very dynamic organelles that constantly undergo fission-fusion processes. Despite the fact that the machinery of mitochondrial biogenesis is well investigated, regulatory mechanisms remain unclear. Dimethylarginine dimethylaminohydrolase 2 (DDAH2) is a poorly characterized protein that is associated with highly vascularised tissues. It has been demonstrated that DDAH2 plays a key regulatory role not only in vascular-associated processes like angiogenesis or endothelial senescence but also in insulin production or immune response. However, the exact mechanism of DDAH2 action remains unclear. Recently, DDAH2 was shown to be able to translocate to mitochondria and mediate mitochondrial fission in macrophages during the innate immune response, thus identifying it as a novel modulator of this highly important biological process. Similar translocation behaviour of DDAH2 was demonstrated upon IL-1β stimulation in human chondrocytes. In the lab, the research group demonstrated DDAH2 translocation in the heart from hypertensive mice. Considering the variety of observed pathological conditions united by a common DDAH2 translocation pattern, the group believes that the fission-regulatory function of DDAH2 might be a universal response to stress.

The goal of the project is to test the hypothesis that DDAH2 plays a regulatory role in the modulation of fission processes in endothelium under various stress factors. Therefore,the involved researchers will make use of human umbilical vein endothelial cells (HUVEC) with knock-out of DDAH2, generated with the CRISPR/Cas9 technology. As a complementary approach, the research team will overexpress DDAH2 in HUVEC cells using expression vectors. HUVEC cells will be stressed with several factors to imitate pathological conditions including angiotensin II to emulate hypertension-associated endothelial dysfunction (ED), OxLDL – atherosclerosis-associated ED, poly(I:C) - viral infection-associated ED. Cell culture work will be performed at the applicant site (TUD). All necessary tools for the generation of transgenic cells and tools for detection of DDAH2 in different systems are available in the lab of the applicant. To determine mitochondrial biogenesis and mitochondrial respiration function of the genetically modified HUVEC cells, work will be performed in collaboration with Dr. Afshan Malik (KCL). The methodological expertise of Dr. Malik’s group includes tests for mitochondrial function (expression of the mitochondrial abundance and biogenesis genes), and measurement of cellular respiration rate with the Seahorse platform.

The research group strongly believes that the results of the project will help to close the knowledge gap in the understanding of the function of DDAH2. Moreover, the obtained results could be potentially implemented into the development of specific mitochondrial-based therapeutic strategies.

Partial funding

The researchers around Riccardo Bassoli and Osvaldo Simeone team up to make the latest achievements of quantum technologies research accessible to PhD students.

The proposal aims at supporting the organisation of a joint TUD-KCL Ph.D. Summer School on quantum communication networks and technologies. These are very timely and relevant topics in the design of future generation networks. These topics are fundamental for enabling resilient and secure Tactile Internet (TI) for applications like eHealth and industrial cobots. This perfectly fits the current objectives of CeTI and TUD-KCL priorities within transCampus research.

The summer school will be on 30th-31st May 2024 and it will consists of 4 internationally well-known speakers (professors) that will be invited to give 3hrs talks. Identified speakers to be confirmed are: Chiara Marletto (University of Oxford), Leonardo Bianchi (University of Florence), Stephanie Wehner (TU Delft), and Angela Sara Cacciapuoti (University of Naples Federico II). These talks will include topics that are fundamental for the design of future quantum-6G networks and they will describe the latest achievements and capabilities of the technologies. For example, system-level characteristics of the Quantum Internet, information theoretic concepts of quantum communications and computing, experimental aspects of the Quantum Internet, and quantum computing for optimisation problems.

The Ph.D. Summer School will be open to Ph.D. students worldwide that research quantum technologies for communication, sensing, and computing. By attending this school they will be able to learn the latest advancements in

• the design of the Quantum Internet
• the current technologies that are going to be used for Quantum Internet realisation
• the information-theoretic concepts applied to design quantum computers and quantum communications
• the quantum computing platforms and the quantum optimisation algorithms that can be used in quantum communication networks

The added value for the Ph.D. students, by attending this school, will be the possibility to meet in person and learn aspects of quantum communication networks from the experts that are designing, realising, and standardising them. The Ph.D. students will be able to have interactive discussions with the speakers and, apart from the lectures given by the speakers, there will be dedicated poster sessions, in which the Ph.D. students will be able to present their works and to network both with other attendees and the speakers. Ph.D. students from TUD-KCL working on quantum technologies and TI will also be encouraged to present their work.

The expected results include:

• strengthening the collaboration of TUD and KCL on quantum communication networks and 6G
• showing the international achievements of TUD and KCL on the topics, also in the context of the transCampus activities
• creating synergies with other well-known international experts for future projects and collaborations
• showing to international Ph.D. students the involvement of TUD and KCL in the topics within the transCampus collaboration and CeTI

In the past years Prof. Cuniberti was a very active transCampus researcher whose project in 2020 has been recognised with the tC research award. This year he collaborates with his colleague Prof. Gao from King’s College London to address the complex process of digitising smell and taste for robotic use.

Designing robots to perform physical tasks and connecting them to their environment by equipping them with special senses is, by its nature, an interdisciplinary task, connecting areas like engineering, computer science and artificial intelligence. Smell and taste provide a wealth of information about our physical surroundings. Despite this important role, the digitisation of both senses is still in its infancy compared to vision and hearing. The development and integration of technological solutions that will ultimately enable the electronic detection of odours as well as of molecular species in liquids is today still a highly challenging problem in research and technology.

To advance in direction of digitising selected special senses, the overarching goal of the project, the partners at KCL and TUD possess ideally matching expertise and experience in robotics and sensor technology. The mission of CORE at KCL is to develop solutions to critical challenges faced in society by the development of robot-centric approaches. The activities include medical topics, horticulture/agriculture, manufacturing, and humanitarian demining and bring together expertise in innovative sensing and manipulation technologies, reconfigurable and flexible metamorphic robotic platforms, variable stiffness and soft-body materials, dynamic control methodologies for multi-robot teams and progressive modes of human-robot integration. With these research topics, CORE ideally complements the activities of the chair of Gianaurelio Cuniberti, the initial TUD partner, on sensor development and integration, with a special focus on digital olfaction and taste, currently still “missing senses” in technical systems. Further partners at TU Dresden will be identified and involved during the project.

Joining forces will boost the innovation potential of both partners, e.g. by developing methods and protocols for the olfactory navigation of robots, which can be used to detect individual gases and to trace their sources in a wide range of applications in challenging environments to be found in industrial manufacturing, security technology, space applications, nuclear technology or in the health sector.

The project will be used to define concrete cooperation topics and additional partners to be involved in the cooperation both at KCL and TUD. The ideas and preliminary results emerging from these extended discussions will be the basis for future joint external funding applications.

After the start of the project first joint research activities, e.g. equipping robotic units at KCL with sensors developed at TUD, are planned to be implemented in Summer 2024. The bundled resources and effort will have an output that will be published in joint papers and used for joint patents leading into sustained joint projects.

Partial funding