Research area: Neuroscience

Cooperative interactions of distributed neuronal assemblies are associated with encoding memories and retaining information that gives rise to appropriate brain functions and behaviors. Recent studies have consistently demonstrated that altered neural
network activity contributes to cognitive impairment during aging and various neurodegenerative diseases, even during preclinical stages before Symptoms are observed in patient neuroimaging exams. Despite increased research efforts, biological
advancement, and pharma-industry Investments to fulfilling the unmet clinical need in the neurotherapeutics field, the low success rate of drug development and cell therapies poses daunting challenges with no cure currently available for Alzheimer's disease (AD) or dementia. Interestingly, other reports generated mounting evidence supporting the profound effect of blood-borne factors in the systemic milieu on stem cell function, revealing new possibilities for promoting healthy aging, reversing aging phenotypes, and delaying the onset of AD with young circulatory rejuvenatingfactors. However, the effects of these systemic environments on neuronal activity and pattern dynamics of adult human networks remain unexplored.

In this transCampus project, the group intends to develop an early predictive platform that harbors the impact of the human systemic milieu on adult healthy human iPSC-derived neuronal networks. We will employ a non-invasive, label-free, multi-site high-density neurochip augmented with artificial intelligent machine-learning analytical methods for monitoring multiplex spatiotemporal dynamics of network-wide activity and connectivity in physiological and pathological models. The platform has the potential to develop serum-based novel therapeutic strategies to promote brain network reorganization in age-related cognitive declines. Also, it will provide network-based biomarkers that could be a diagnostic entry point for understanding neuromodulation and communication mechanisms underlying computational neural dynamics in physiological and pathological states.

Completely funded.

Research area: Mathematics

The transCampus Professors Anita Behme (TU Dresden) and Markus Riedle (King’s College London)s have received a DFG grant for their project "Ornstein-Uhlenbeck processes driven by cylindrical Lévy processes" which includes a  3-year PhD studentship. The planned tandem supervision and studies at both locations will provide the PhD student with the experience of internationally competitive research at two leading universities and other top universities in London (LSE, Imperial College, UCL), and with the opportunity to develop an international network. DFG fully funds the 3-year PhD studentship jointly supervised by the PIs, but although the project is strongly motivated by offering the PhD candidate an international education within the TransCampus initiative, induced higher costs of studies abroad could not be covered by DFG as outside of Germany. Therefore, the transCampus provides complementary funding.

The project, which was stimulated by the synergy effects of the transCampus initiative, is based heavily on the different research areas of the two supervisors: Prof A. Behme’s expertise is rather in modelling of random dynamical systems, whereas Prof M. Riedle mainly works on stochastic analysis in infinite dimensional spaces. The PhD student will focus on modelling aspects of the project during her time in Dresden, whereas she will concentrate on the analytical part during her stay in London. The PhD project "Ornstein-Uhlenbeck processes driven by cylindrical Lévy processes" studies a complex dynamical system evolving in time and space and subject to a random perturbation. Such models arise naturally in various fields such as engineering, economics, population dynamics, meteorology, physics and seismology among many others. The reasons for the random perturbation might be found in external or internal fluctuations, not allowing a deterministic description, in random events in the future, or in uncertainty of the model. However, up to now, modelling the random perturbations has been restricted to rather regular processes, e.g. with continuous trajectories or with regular distribution in time and space, although statistical evidence, experimental observations or realistic constraints require the perturbation by a highly irregular process such as a cylindrical Lévy process. One might just think of the sudden slip on a fault which causes an earthquake.

Completely funded.

Research Area: Industrial Management & Systems Engineering

Young researchers, starting their academic careers as PhD students, post doctoral fellows, or assistant professors, often face significant challenges when disseminating their results in highly recognized international scholarly journals. They often lack the writing skills expected (from their peers and leading journals), the culture of their research community, and the good connections to the practical fields they are investigating. The proposed cooperation between King's College London and TU Dresden will focus on helping young academics disseminate their research output and expose them to emerging real life rich manufacturing problems. The goal of the cooperation partners, Rym M'Hallah (Department of Engineering, esp. Systems Engineering, KCL) and Udo Buscher (Chair of Business Administration, esp. Industrial Management, TU Dresden), is to design and conduct a cross-site workshop for the purpose. The workshop will target young researchers in Operations Research (OR) and Industrial Management/Engineering, mainly from KCL and TU Dresden, but will also be open for international participants. This will not only expand the impact of the workshop and networking activities of academics, but will establish the best practices and guidelines that other schools and departments might adopt to support and promote young researchers’ careers. It may become a model for yearly summer schools, with a larger target audience.

The proposed workshop will be preceded by an online series of meetings of the junior academics with their respective mentors. Each participant will bring their current working status of a research paper and identify potential improvements they would like to implement during the workshop. Ideally, the paper should be in the final submission stage or a manuscript that has been submitted to a journal but requires revision.

The workshop itself consists of two parts, each spanning 4 days and 4 nights. The first part will take place at KCL and will focus on the essential elements of writing a good paper that is publishable in an international, highly recognized OR journal. It consists of interactive learning events, networking opportunities, discussions with leading scholars, mentoring on academic careers, lectures by leading editors and scholars, and young academic presentations of their papers and their milestones.

The second part of the workshop will take place at TU Dresden after a work phase of about two months from the end of the first part. This second part will focus on two aspects: (1) Enhancements made during the work period, rebuttals to Reviewers, and submitting a paper; (2) Linking theoretical research to real-life practical problems in order to enhance their implementation and to better serve the industry. Therefore, the attendees will not only be involved with active learning sessions and presentations of their work but will also participate in field visits to selected companies.

Partially funded.

Research area: Materials sciences & physics

Since the first experimental demonstrations of the Chirality Induced Spin Selectivity (CISS),  CISS has gained much interest in various scientific fields recognizing the broad impact it bears in areas such as nanoscale charge transport, spintronics, (bio)chemical reactions and (bio)chemical recognition. In brief, when an electron  circulates along a chiral molecular backbone, the particular helicoidal potential imposed by the chiral structure enhances the scattering of one of the electron spins over the other, resulting in the generation of a spin-polarized current. The experimental observations point at various factors playing an important role in controlling the CISS effect such as the molecular length, the temperature, and the direction of the intrinsic molecular dipole moment, to mention the most relevant ones. In a previously funded transCampus Joint Research Award, the group addressed the influence of the intrinsic electrical dipole moment on the resulting spin polarization in helical peptides. The current proposal aims at extending the experimental and theoretical investigations (now strengthened  through the participation of Prof. L. Kantorovich from KCL) to address the influence of temperature and of  molecular length on the CISS effect.  This will give us further insight  for rationalizing the mechanisms of spin selectivity  in chiral molecules, and it will open the possibility  to elaborate  methodologies for designing hybrid electrode/molecule interfaces using chiral molecular systems for room-temperature spintronics applications. The concepts learnt here will further help understanding the role of homochiral motifs recurrently exploited in biological systems in topics such as local magnetic fields affecting enzymatic reactivity and/or the possible role of spin-polarized currents in the long-range electron transfer/transport in biology.

Partially funded.

Research area: Physiology & Engineering

Space exploration has been a fascinating endeavor for mankind for decades. Be it the motivation to establish a base on the moon in order to be able to prepare long-term missions to other planets and celestial bodies. Or it is the vision to land on Mars, which is not only relatively close to Earth, but also quite similar to our planet. This is very appealing for both scientific exploration and human settlement. In addition, this would allow for a better understanding not only of our own planet, but also of the evolution of other planets in our solar system. However, for successful exploration missions, technology and equipment must not only be designed to function reliably in the harsh space environment, but more importantly, we must understand how the human body, especially that of astronauts, will respond. Understanding how human physiology is affected by space and different gravity fields is therefore important not only for astronaut safety, but also for successful missions. Yet, there is a lack of reliable data on physiological measurements in space and its harsh environments. Although exploration of space and related topics has been underway for decades, much more needs to be done, especially given the underlying motivation to go to Mars and establish colonies on the Moon. This project therefore aims to establish the foundations for understanding human physiology in space-related environments through international collaboration among transCampus partners.

Partially funded.

Research area: Electrical Engineering

Large-scale grid integration of renewable energy sources and higher flexibility to meet volatility in energy production and demand (e.g. by storage systems) play a major role to shape the electricity network of the future. Therefore, network operators in Europe (including Germany and UK) but also all over the world face similar challenges to integrate those modern installations and devices into the grid at all voltage levels from low voltage (distribution network) to extra-high voltage (transmission system). All those installations are connected to the electricity network via a power electronic interface, which can detoriate the quality of the supply voltage, mainly due to harmonic distortion. In order to ensure a reliable operation of devices and installations connected to the electricity network, network operators have to manage the harmonic distortion by setting appropriate limits. In transmission systems harmonic simulations are an essential tool to determine the impact of installations and to coordinate their emission in order to utilize the harmonic hosting capacity of the network as efficient as possible in order to minimize costs for possible mitigation. Such simulation requires reliable models of all relevant components, where especially the aggregate modelling of downstream distribution networks is still a challenging issue without any satisfactory solution yet. This is also confirmed by both the UK transmission system operator as well as the German transmission system operators and forms the basis for the proposed project.
Both applicants have already first experiences in modelling aggregated equivalent models of distribution networks from different projects in their countries. The objective of this project is to compare the modelling approaches and to identify the impact of the model parameters on the results of harmonic simulations in transmission systems. The study is based on a reference network that has been developed by TUD. Based on the complementary work on this project combining the expertise of both universities, an improved modelling approach is proposed. The results of the project are presented to the relevant stakeholders (transmission/distribution system operators) of both countries in a workshop that is held in Dresden. Further, a joint conference paper is developed and the findings of the study shall serve as basis to strengthen the collaboration between the applicants and to develop a joint research project proposal.

Partially funded.

Research area: Cardiovascular medicine

Cardiovascular remodeling in response to hypertension is a not fully understood process  associated with structural and functional changes in the cardiomyocytes, endothelial cells, smooth muscle cells, and in the extracellular matrix. Initially it  promotes adaptation to the increased pressure overload, but  may lead to heart failure and vascular stiffness-mediated end organ damage, if continued. Increased rate of mitochondrial fission, with dynamin-related protein 1 (Drp1) being the key player, has been recently proposed as a key contributor to development of  myocardial and aortic remodeling. A newly identified regulator of innate immunity dimethylarginine dimethylaminohydrolase 2 (DDAH2) has been recently shown to promote mitochondrial fission by phosphorylation of Drp1. Our pilot studies showed that DDAH2 is strongly expressed in mouse heart and aorta and gets translocated into mitochondria after infusion of angiotensin II. The goal of the current proposal is to test the hypothesis that DDAH2 plays a major role in regulation of cardiovascular remodeling in hypertension by modulating mitochondrial fission via the DDAH2-Drp1 signaling pathway. We hypothesize that deletion of DDAH2 will attenuate both myocardial and aortic remodeling. Specifically, we will investigate the role of DDAH2-Drp1 in mediation of angiotensin II-induced mitochondrial fission and cardiovascular remodeling in mice and cultured endothelial and smooth muscle cells. We will also perform proteomic analysis with the aim to identify new targets involved in the metabolic pathways leading to remodeling.

Completely funded.

Research area: Haematology

Background: Myelodysplastic syndromes (MDS) represent a heterogeneous group of haematological diseases that manifest themselves through ineffective blood cell maturation in the bone marrow. Mutations in splicing factors are commonly seen in MDS, yet the specific inflammatory pathways activated by mis-splicing have not been fully elucidated. Altered RNA splicing of inflammatory and immune genes may contribute to MDS pathogenesis by leading to inflammation, changes in immune cell function, and increased risk of infection. Recent data suggest that driver mutations in splicing factors SF3B1 and U2AF1 induce a targetable overactive IRAK-4-L isoform that operates at the junction of multiple inflammatory pathways in innate immunity (Choudhary et al. 2022; Smith et al. 2019). Interestingly, published RNA-seq datasets on SF3B1-MDS implicate much broader splicing abnormalities in major downstream pro-inflammatory cytokine genes including IL1B and IL18 (Kesarwani et al. 2017). Thus, while IRAK-4-L facilitates the activation of pro-inflammatory gene expression programmes, the induced genes themselves may be subject to mis-splicing with implications for the overall inflammatory outcome.
From a clinical perspective, the potential of cytokine-targeted anti-inflammatory therapies in these patients is unclear. Identification of inflammatory splicing signatures will aid future stratification of patients for novel therapeutic approaches currently being evaluated in clinical trials. With this project, the partners will follow up on the shared vision of integrating the “Immunome” in the stratification of MDS (Winter et al. 2020). The project will combine the expertise of Dr Kordasti’s group in the analysis of large single-cell datasets on the immunobiology of haematological malignancies and Dr Winter’s in the immune dysregulation of MDS.

Objectives: This transCampus project aims at investigating at the single-cell level the genome-transcriptome relationship in SF3B1- and U2AF1-mutated MDS focusing on innate immune mediators, in particular caspase 1-processed pro-inflammatory cytokines and related inflammatory pathways. Secondly, the scientists want to focus on splicing signatures affecting myeloid cell differentiation in splicing factor-mutant MDS.
Milestones: (I) Single-cell RNA-seq of selected splicing factor-mutant MDS samples and healthy controls (TUD), (II) Bioinformatic analysis of single-cell RNA-seq data through computational pipeline (King’s), (III) Integration of clinical data (TUD), (IV) Application for future joint funding (TUD, King`s)
Expected results: Single-cell RNA-seq has the potential to facilitate isoform quantification of a given gene as the confounding factor of a mixed population of cells is eliminated. We expect that single-cell RNA-seq of splicing factor-mutant MDS samples will reveal how these mutations affect inflammatory programmes along distinct stages of myelopoiesis. It is also expected that the work will inform on the potential of cytokine targeting in MDS patient subgroups.

Completely funded.