Research projects in NanoBioMed

In the numerous third-party funded projects in the focus area “NanoBioMed – Life and Matter”, scientists at the UdS are conducting research on important questions in the fields of medicine, physics, biology, and chemistry.

Below is a selection of current NanoBioMed research projects funded by the German Research Foundation (DFG), the European Commission or the German Federal Ministry of Education and Research.

 

German Research Foundation (DFG)

The NanoBioMed focus area is home to one Collaborative Research Center (CRC) and two CRC/Transregios (CRC/TR), in which several universities work closely together. In addition, the German Research Foundation funds two research groups and an Emmy Noether junior research group in the focus area.

 

 

Collaborative Research Centers (CRCs)

CRC/TRR 152: Maintenance of Body Homeostasis by Transient Receptor Potential Channel Modules
  • Subject classification: Medicine
  • Project management: Prof. Dr. Ulrich Boehm (Experimental and Clinical Pharmacology and Toxicology)
  • Funding period: 2014-2026
  • Speaker University: LMU München

Transient receptor potential (TRP) channels represent a diverse protein family with salient roles as versatile cellular sensors and effectors. TRP proteins control an exceptionally broad spectrum of homeostatic physiological functions, illustrated by more than 20 hereditary human diseases caused by mutations in 11 Trp genes. Most TRP channel-related human disorders impinge on development, metabolism and other homeostatic functions. However, a detailed understanding of the underlying pathophysiology is missing. There is accumulating evidence to link TRP channels to even more human diseases beyond TRP channelopathies, and accordingly, TRP proteins have been identified as appealing therapeutic targets.

The research of the CRC will help overcome a merely genetic classification of TRP channels by means of physiologically relevant functional criteria, thus leading to a functional re-definition of what is presently called the “TRP channel family”. Such fundamental insight will furthermore open up new avenues for specific, tailored treatment options for patients suffering from diseases inflicted by dysfunctional TRP proteins.

Homepage of CRC/TRR 152

CRC/TRR 219: Mechanisms of Cardiovascular Complications in Chronic Kidney Disease
  • Subject classification: Medicine, Biology
  • Project management: Prof. Dr. Danilo Fliser (Internal medicine)
  • Funding period: 2018-2025
  • Speaker University: RWTH Aachen

The aim of this Transregional Collaborative Research Center TRR219 is to analyze in experimental and clinical studies the multi-factorial aspects of CKD-related cardiovascular morbidity and mortality caused by alterations in the circulation and the myocardium.

In addition to examining pathological mechanisms affecting the cardiovascular system in CKD at the basic science level, we will also study the translational aspects by analyzing novel interventions and diagnostic tests in the context of CKD-related cardiovascular pathology.

Homepage of CRC/TRR 219

 
CRC 1027: Physical modeling of non-equilibrium processes in biological systems
  • Subject classification: physics, biology, chemistry, medicine
  • Speaker: Prof. Dr. Heiko Rieger (Statistical physics)
  • Funding period: 2013-2024

CRC 1027 is an interdisciplinary research team with the goal of gaining a quantitative understanding of the physical mechanisms at work in the self-assembly of biological matter into complex structures. This self-assembly enables biological systems to carry out dynamic functions such as cell migration and polarization, cell-cell adhesion and synaptic transmission, biofilm formation, and tissue growth. The project analyzes the ways in which large biological molecules and cells physically interact, exert forces, move one another, and self-organize into complex functional patterns at all levels, from proteins, lipid membranes, and cells to biofilms and tissues.

Homepage of CRC 1027

 

Other Projects funded by the DFG

FOR 2688: Instabilities, Bifurcations and Migration in Pulsating Flow
  • Research Unit
  • Subject classification: Thermal engineering / Process engineering
  • Speaker: Prof. Dr. Christian Wagner (Experimentalphysik)
  • Funding period: seit 2019

The way blood flows through the vessels plays a major role in the development of cardiovascular diseases, such as thrombosis and arteriosclerosis. However, the physical principles of blood flow are poorly understood. Blood is more heterogeneous than water is and is driven by a pump, the heart, it pulsates. Previous experiments on flow behavior, however, have generally been based on water moving uniformly. An interdisciplinary team from physics, engineering and medicine from several universities want to close this knowledge gap. Together, they are working on this goal in the newly established Research Unit "Instabilities, Bifurcations and Migration in Pulsating Flow".

Homepage of the Research Unit

Emmy Noether Independent Junior Research Group: Hybrid Functionals for Hybrid Materials
  • Emmy Noether Independent Junior Research Group
  • Subject classification: Physical and Theoretical Chemistry
  • Project leader: Hilke Bahmann (Physikalische und Theoretische Chemie)
  • Funding period: 2019-2024

Computer-aided simulation of single molecules, also called molecular modeling, is used in basic research and increasingly also in industry to find new materials, develop more efficient catalysts or improve medical agents. Often microscopic effects at the subatomic level are crucial for macroscopic properties, so a reliable and accurate description of the electron structure is an important prerequisite for the studies mentioned above. Electron structure can be calculated by various quantum chemical methods, with density functional theory being the most popular. Two currently important limitations of the available density functionals are constant, system-dependent parameters and an insufficient description of strong correlation effects between electrons.

To improve the predictive power of density functional theory for model systems of heterogeneous catalysis and hybrid materials, this project will develop several methods that adapt to the local electron structure and incorporate additional physical quantities to explicitly describe strong correlation. A second important aspect is the efficient implementation in a renowned quantum chemical program package, so that the new methods can be directly applied to chemically and physically relevant systems and are available to a broad user community.

European Commission

The following research projects in the NanoBioMed priority are funded by the European Commission and coordinated by Saarland University. This also includes the various grants from the European Research Council (ERC).

 

European Research Council (ERCs)

ATTACK – Analysis of the T cell’s Tactical Arsenal for Cancer Killing
  • Horizon 2020 – ERC Synergy Grant
  • Project leader: Prof. Dr. Jens Rettig (Cellular neurophysiology)
  • Funding period: 2021-2027

Within the framework of this ERC Synergy Grant, an international team is researching the latest approaches in the fight against cancer cells. The focus is on so-called supramolecular attack particles (SMAPs), which are used by the body’s own defense cells (T cells) against tumor cells.

For this, the consortium will analyze the so-called supramolecular attack particles (SMAPs), which are part of the T cells’ arsenal in the fight against tumor cells. The participating scientists in Homburg will analyze the exact release of SMAPs by the T-cells, scientists in Sienna will investigate the production of SMAPs, while the British scientists in Oxford will investigate the mode of action of the particles. And finally, the French research group in Toulouse will analyze how the tumor cells react to the attack by SMAPs. The consortium envisions that SMAPs will be freeze-dried and shipped around the world, solving problems related to current immunotherapies, leading to global health impact.

Homepage of ATTACK

 
CROSSTALK – Opposites attract: Crosstalk between vimentin and microtubules - mechanical stability vs. dynamic adaptability

Human cells are marvels of nature: They can squeeze through narrow pores, for example, but at the same time they are very stable. Two components of the cytoskeleton play an important role here: rigid microtubules and flexible intermediate filaments. How these two components interact with each other has been little explored. Laura Aradilla Zapata will receive 1.5 million euros from 2024 as part of an ERC Starting Grant.

MemDense – Cellular control of membrane protein crowding
  • Horizon 2020 – ERC Consolidator Grant
  • Project leader: Prof. Dr. Robert Ernst (Medical Biochemistry & Molecular Biology)
  • Funding period: 2020-2025

The endoplasmic reticulum (ER) is a complex organelle in terms of both structure and function. It is the largest membrane-bound intracellular compartment, spanning a network of tubules and sheets. The ER plays a critical role in the synthesis of secretory and membrane proteins, their folding, modification, and maturation. At the same time the ER is a major hub for the biosynthesis and distribution of phospholipids and sterols. Dysfunction results in ER stress and a failure to fold soluble and membranes proteins, thereby activating the unfolded protein response (UPR). The UPR is critical to re-establishing homeostasis. Until now, the UPR has been studied with a focus on the role of soluble proteins, whereas the more abundant membrane proteins have been largely overlooked. All that is changing with the EU-funded MemDense project, which studies the role of the density of ER membrane proteins and their misfolding in adaptive responses.

Homepage of MemDense

MinSynCell - Unravelling the chemical-physical principles of life through minimal synthetic cellularity

A grand challenge in bottom-up synthetic biology is to design and construct synthetic cells with life-like properties from a minimal number of parts. Achieving this goal would be a major engineering feat and enable an understanding of how living systems work from the perspective of physical chemistry. Towards this, we have exploited bottom-up approaches and generated new insights into the impact of compartmentalization on the thermodynamics and kinetics of incorporated enzyme reactions. Our findings that dynamic coacervation can ignite dormant enzyme reactions provides the conceptual framework for our plan to build sustained out-of-equilibrium synthetic cellular systems. In MinSyn, the aims are to:

  1. Define how molecular reaction networks are tuned by compartmentalization.
  2. Build minimal synthetic compartments with self-sustained, out-of-equilibrium behaviour.
  3. Utilize communication to coordinate reaction networks within populations of cells.

Together, these objectives test our overarching hypothesis that sustained out-of-equilibrium systems can be established by interconnecting three features: molecular reaction networks, compartmentalization and communication. Key to this endeavour is our unique combination of chemical, biochemical and biophysical tools for quantitative characterization of synthetic cellular systems. We are primed to address the major engineering challenge of building sustained out-of-equilibrium synthetic cellular systems and to tackle a central problem in biological sciences: “How do biological cells and tissues sustain life from collections of non-living molecules?” Our interdisciplinary approach will provide novel tools to the community and represents a unique multidisciplinary approach that will ultimately define the chemico-physico parameters of life. This can lead to unprecedented opportunities to rationally engineer molecular systems which may supersede biological capabilities.

More information about MinSynCell

Other projects funded by the EU

SafePolyMed – Improve Safety in Polymedication by Managing Drug-Drug-Gene Interactions
  • Horizon Europe – Health
  • Project lead: Prof. Thorsten Lehr (Clinical pharmacy)
  • Funding period: 2022–2025

Adverse drug reactions (ADRs) are a major burden to our healthcare and economic systems. In Europe alone, approximately 197,000 annual deaths can be attributed to ADRs. The regular use of five or more medications at the same time (polypharmacy), the coexistence of two or more long-term medical conditions or diseases (comorbidity), and genetic diversity have a significant effect on drug efficacy and consequently, raise the incidence and severity of ADRs.

Aiming to increase overall drug treatment safety, the international team of the EU research project SafePolyMed seeks to provide physicians and pharmacists with innovative tools to define, assess and manage drug interactions, especially the so-called drug-drug-gene interactions (DDGIs).

Overall, the envisioned tools will not only empower healthcare providers but will also educate patients and citizens on how to adequately and safely manage their drug treatments.

Homepage of SafePolyMed

 
TALENTS – Training AlliancE for Novel Microbiome-Modulating TherapieS
  • Horizon Europe – Marie Skłodowska-Curie Actions (MSCA)
  • Funding period: 2023–2027

TALENTS is an international doctoral program of Saarland University, sponsored by the Marie Skłodowska-Curie COFUND-Action of the European Commission. It brings together 15 doctoral candidates (DC’s) to work for their PhD degree at the interface of pharmacy, chemistry, biology, medicine and bioinformatics in an interdisciplinary training alliance.

The overarching aim is to investigate and exploit the human microbiota to fight diseases. Saarland University is named by this federal state of Germany, located near to France and Luxemburg. The TALENTS graduate school bridges the main campus in Saarland’s capital Saarbrücken with the medical campus and University Hospital in the city of Homburg.

Homepage of TALENTS

 
Further projects

German Federal Ministry of Education and Research

The following research projects in the NanoBioMed focus area are currently funded by the German Federal Ministry of Education and Research (BMBF).

 
FUMBIO | Collaborative project: Biotechnological fumarate value chain - From CO2 and sugar to biodegradable chemicals - Subproject: Systems biotechnology and process development (iSBio)

With the FUMBIO project, we are addressing the increasing demand for bio-based chemical products with a good ecological profile by developing a new, sustainable "fumarate value chain".

Based on fermentation, this is intended to replace the chemical synthesis of fumarate from fossil raw materials. The new process uses two main starting materials: CO2, which is obtained from chemical processes, and sugar (e.g. glucose), which is produced by plants from CO2. This means that the expected carbon footprint of fumarate and other downstream products is significantly lower or even negative compared to standard petrochemical-based processes. Furthermore, we will develop biocatalytic routes to further utilise the fermentation-based fumarate for the production of biodegradable chemicals, such as complexing agents and polymers. Both are high-volume product groups (>200 kt/year), so there is significant potential to improve sustainability.

With FUMBIO, we want to show the complete value chain from the raw materials to the end product and evaluate the environmental impact and CO2 footprint as part of a life cycle analysis. The consortium of experts from the fields of metabolic engineering, systems biotechnology, biochemistry, bioprocess development and life cycle analysis (Philipps University Marburg, Saarland University, Rhineland-Palatinate Technical University Kaiserslautern-Landau, BASF) has all the necessary tools and expertise to achieve the outlined goals. We expect short development times, a high technical probability of success despite a significant need for innovation, competitiveness and high sustainability as the basis for successful commercial realisation.

HiFi - Highly stable, broadband quantum frequency converter with two-stage conversion

To connect quantum nodes to quantum networks, the frequencies or wavelengths of individual photons must be specifically adapted to the standard of the communication channel (quantum frequency conversion). In the HiFi project, quantum frequency converters and the underlying basic technologies are being systematically developed.

For this purpose, expertise from the fields of quantum technology, optics, laser, fiber, automation, assembly, interconnection and production technology is brought together. In addition to the AG Quantenoptik at Saarland University, five other partners are involved in the project. It is led by Menlo Systems GmbH.

Homepage of HiFi

Myxo4PUFA-2 – Sustainable production of omega-3 fatty acids based on myxobacterial genes

Omega-3 fatty acids play an important role in our diet. They promote brain development, especially in newborns, improve blood circulation and protect the joints. Recent studies confirm that docosapentaenoic acid (DPA) and eicosatetraenoic acid (ETA) in particular have a health-promoting effect. Due to the low contents, conventional extraction processes based on fish oils are not suitable for obtaining n-3 DPA or ETA. In collaboration with the Saarland biotechnology company MyBiotech and the team of Rolf Müller (Helmholtz Institute for Pharmaceutical Research Saarland), the project aims to develop a novel production process for rare omega-3 fatty acids such as DPA and ETA. Newly discovered biochemical synthesis pathways should enable the efficient production of these complex molecules in microorganisms. The project is working on the development of customized cell factories in the non-conventional yeast Yarrowia lipolytica for the targeted synthesis of the new products, as well as on the development of fermentation processes for their production.

Homepage of Myxo4PUFA-2

NiQ - Noise in Quantum Algorithms

The project will develop quantum algorithms that benefit from noise. A conceptual framework will be developed in which quantum algorithms are understood as a self-organizing process with an interplay of noise and coherent quantum dynamics.

The project is led by Saarland University. In addition, the Freie Universität Berlin, the Forschungszentrum Jülich, the Deutsches Elektronen-Synchrotron, Qruise GmbH, and IBM Research Europe as an associated partner are also conducting research here.

Homepage of NiQ

QPIC-1 - Photonic Integrated Quantum Computer

Compared to classical computers, quantum computers can perform complex calculations much more efficiently. Thanks to this speed advantage, problems can become computable that are considered unsolvable with classical computers. For practical applications, however, systems are needed that can work with a significantly larger number of quantum bits (qubits) than previously possible.

In QPIC-1, a novel platform for a quantum computer will be developed using single light particles (photons) as qubits. This requires both novel sources to generate quantum light and integrated photonic circuits in which the information processing takes place. The work and developments in QPIC-1 are intended to make quantum computers practical for real applications.

The project is coordinated by the Technical University of Munich. In addition to Saarland University, six other partners are working in the joint project.

Homepage of QPIC-1

QR.X - Secure fiber-based quantum communication

Quantum communication makes a decisive contribution to the secure transmission of data. Over long distances, however, current quantum communication is reaching its limits. Quantum repeaters are needed to overcome these limits. Novel quantum repeaters will be implemented in QR.X and tested under real conditions. The project makes an essential contribution to the development of quantum communication infrastructures for the tap-proof transmission of data. A total of 25 institutions from Germany are working together on this project, including universities, research institutes and companies.

The project is coordinated by Saarland University (Christoph Becher).

Homepage of QR.X

QuFabLab - Quantum Technology FabLabs: Make, Learn, Share

QuFabLabs creates an education and collaboration ecosystem in the field of quantum sensors. Competence building, development of specialists and interdisciplinary collaboration for sensor systems of the second quantum generation in mechanical and plant engineering are in the foreground.

The joint project is led by the Hochschule Ruhr West/Institut für Informatik Bottrop. In addition to Saarland University, the Hochschule Niederrhein/Competence Center FAST, the Fraunhofer Institute for Microelectronic Circuits and Systems, and w.i.r.i. e.V. are also involved in project implementation.

Homepage of QuFabLab

 
VOMBAT - Miniaturized entanglement source in the telecom sector based on AlGaAs Bragg reflection waveguides

The aim of the project "Miniaturized entangled photon source in the telecom sector based on AlGaAs Bragg reflection waveguides (VOMBAT)" is to develop a source for entangled photon pairs in which the required pump source and the generation of the entangled photon pairs are integrated in one chip. For the generation of photons with frequencies corresponding to low-loss telecommunication, a photon pair source based on the material system AlGaAs will be designed and fabricated. For the distribution of the photon pairs to the different receivers or frequencies, it is investigated how this can be done as compactly as possible in an integrated photonic circuit in which the chip-integrated photon pair source is embedded. The technological requirements for later commercial exploitation are also being investigated. The overall system will be tested in an existing fiber optic link.

The project is coordinated by the Fraunhofer Institute for Telecommunications. In addition to Saarland University, two other partners are working on the joint project.

Homepage of VOMBAT

Other funding

ANTIPOLE - Antivirals for preemptive therapy of BK polyomavirus infection in transplant recipients and interference with in-host virus evolution

Reactivation of a latent viral infection poses a significant risk to immunocompromised patients in transplantation medicine. BK polyomavirus (BKPyV) is a poorly understood virus that causes nephropathy or hemorrhagic cystitis in a significant number of renal or allogeneic hematopoietic stem cell transplant recipients. Currently, there is no vaccine and drugs are urgently needed for preventive treatment to prevent organ damage. This interdisciplinary project addresses the major challenges that have hindered drug development against BKPyV. The project team synergistically combines specific expertise in small DNA virus immunology and cell biology, cutting-edge genomics, and translational drug discovery to identify drug candidates from unique compound libraries that disrupt key viral processes. The team has developed a novel BKPyV replication assay for drug screening and will use complex human 3D culture models for preclinical validation, such as BKPyV-infected organoids of the proximal renal tubules, organotypic 3D cultures with integrated immune cells, and organ-on-a-chip models. To gain molecular insights into the evolution of drug resistance and develop counterstrategies, researchers will use innovative BKPyV-specific next-generation sequencing technologies to monitor viral genetic adaptation and evolution in the host. With these combined approaches, the team hopes to advance both a straightforward translational approach to drug repurposing in transplant patients and the development of entirely new classes of drugs against BKPyV.

Calcium channels and calcium signals as target for lymphoma therapy

The first-line therapy of diffuse large B-cell lymphoma (DLBCL) is a combined administration of different antibodies and poly-chemotherapy (R-CHOP, Pola-R-CHP). Natural killer (NK) cells play a key role as major mediators of rituximab (R)-mediated cytotoxicity. NK cytotoxic efficiency depends on intracellular calcium signals mediated by Orai/CRAC calcium channels.

We have uncovered a calcium optimum for cytotoxicity, with lower and interestingly also higher calcium signals being less efficient. To analyze calcium signals and cytotoxic efficiency of single NK-cells during apoptotic or necrotic killing of single lymphoma cells in parallel, we have developed single cell cytotoxicity assays with high resolution and automated analysis. Our project aims to analyze whether and how calcium signaling in NK-cells affects the serial killing efficiency of lymphoma cells in the presence of R-CHOP or Pola-R-CHP.

We want to understand whether targeted modulation of calcium signaling in NK-cells, e.g., by Orai channel blockers, could have a therapeutic advantage for the treatment of DLBCL, and whether calcium channels and calcium signaling could represent a target for lymphoma therapy.