Dr. Nevena Tomasevic
The high demand for raw materials is pushing companies to expand their exploration projects into regions that are difficult to access and cost-intensive, such as the deep sea or icy areas. At the same time, the decline in resource prices is forcing companies in the oil and gas sector in particular to minimize their costs and financial risks. As part of the Innovation Grant project, Dr. Tomasevic developed a framework for making realistic predictions about the distribution of sedimentary rocks in so-called "basins”. This framework incorporates specific knowledge, such as sediment erosion, transport, and deposition from source to sink. This development can be useful for narrowing down the search for hydrocarbon-bearing strata. After one year, the project was terminated prematurely, as Dr. Tomasevic has received a call as a Junior-Professor at a German University and will continue this work as the main focus of her future research group.
Dr. Barbara Bergmann
The project aimed at developing a screening method to support police officers in assessing the criminal risk of young offenders. With the help of a screening sheet of empirically proven risk and protective factors for delinquent behavior, police officers were to be given a helpful structure with which they could for the first time gain a comprehensive and balanced picture of the young persons, their personality and their life background. The risk assessment based on the screening sheet can form the basis for further decisions and recommendations by the police officers and, in the further course of the juvenile criminal proceedings and the related risk management, can also benefit the public prosecutor's office and the youth welfare service. The project was carried out in cooperation with state criminal investigation departments of several German states and supported by representatives of the German Association for Juvenile Courts and Juvenile Court Assistance (DVJJ). Beyond the transfer goals set in the project, Dr. Bergmann was able to successfully apply for a position at a state criminal investigation office.
Dr. Wolfgang Fuhl
There are innumerable applications for algorithms from machine learning, especially in the field of automated image analysis. The training is based on ground troth data, which have to be annotated. This annotation requires a considerable amount of time, since it is usually done manually. In this project, a prototype annotation software already developed during the PhD was extended for the automated annotation of structures in image data. The extensions include automated detection, shape determination, classification, value regression, and segmentation. In all application areas, the models are optimized independently by the framework. Finally, the framework can also generate automated real-time detectors, which can be integrated into arbitrary software.
Due to the good collaboration with an industrial partner, a PhD position is now funded within the framework of an industrial partnership and there will be several follow-up projects. In addition, large data sets have been made available to the research community through numerous publications.
Dr. Stefanie Maurer
Disseminating tumors are among the major challenges in clinical oncology and mostly there remain no curative options. One of the main problems is that patients aquire resistance to available therapeutic agents. The number of new drug approvals in oncology is declining since the development and production of novel therapeutics is highly cost and time consuming as well as risky. Receptor Activator of Nuclear Factor κB and its ligand (RANK/RANKL) are mainly known for their role in bone metabolism, where RANKL activates osteoclasts thereby mediating reduction of bone. Meanwhile, a RANKL-neutralizing antibody termed denosumab has been approved for treatment of benign and malignant osteolysis. Platelets express RANKL (platelet-derived, pRANKL) upon activation, which stimulates the cognate receptor RANK that is expressed on tumor cells, thereby facilitating metastasis and chemotherapy resistance of tumor cells. These effects can be overcome by neutralization of RANKL e.g. with denosumab. Within the Innovation Grant project, the influence of (p)RANKL on metastasis and chemotherapy resistance of various tumor entities was be characterized in detail. During the project period, Dr. Maurer was able to conduct research that led to two project-related publications. With the help of the data sets generated, further investigations are being sought which could lead to an application for an indication extension for the substance denosumab. Dr. Maurer has received a consecutive financing for her project and transferred to a University abroad.
Dr. Jacqueline Wettengel
Site-directed RNA editing is one of the emerging technologies that enable reprogramming of genetic information at the RNA level. The aim of this project was to define the parameters that further optimize targeted A-to-I RNA editing using chemically modified guideRNAs. Optimal properties of chemically stabilized guideRNA were determined to induce high editing efficiency, potency, nuclease stability, and low toxicity and immunogenicity. Another goal was to generate solid data to apply for an animal testing license. This required the finding of a suitable endogenous mouse target and editing it efficiently to be able to show that murine ADARs can be recruited as efficiently with chemically modified guideRNAs as human ones.
From the results of the chemical modification patterns and guide RNA sequences, an international patent application was filed together with the technology transfer office.
Dr. Maximilian Priester-Lasch
Based on ethnological research results, the project developed an adaptive consulting concept to support Indo-German cooperation in the private sector. The consulting concept supports companies and organizations in implementing change processes. In the course of this, intercultural misunderstandings are identified, solution strategies are developed and processes are designed to prevent future probleDr. The conception uses concepts and models of human resources, organizational and leadership development and expands them with ethnological insights. Employees are accompanied and trained to be able to deal with intercultural challenges on their own.
A pilot of the project took place in June and July 2019 in a company in New Delhi. A follow-up project initially had to be suspended as a result of the Corona pandemic. Due to the resulting uncertainties, the planned startup was put on hold. Instead the project was initiated in cooperation with a company that was already familiar with the development of the consulting concept.
Dr. Tobias Fabian Schrodt
The aim of the Innovation Grant project was to create a prototype of a new type of artificial intelligence (AI) for controlling computer game characters and a corresponding multiplayer game for mobile devices. The peculiarities of AI characters equipped with this AI are their multiple learning abilities that unfold in a cognitively realistic way while playing. The game is intended to be a first showcase application for this type of AI. During the project period, a prototype was developed and tested by players. Based on the feedback, improvements were made to the game controls and game perspective, and a tutorial was added. In October 2020, a startup company was founded which is now producing the game "Marbles AI". Follow-up funding was secured, among others, through the German Computer Game Funding.
Dr. Shahram Eivazi
During the funding period, work was done on several navigation systems for surgical microscopes in which settings can be controlled by head and eye movements. The goal was to develop and test a surgical microscope for commercial use that works with augmented reality. During the two years, major developments could be implemented on both software and hardware and the project was presented not only at several events but also to various companies which led to the succesful tranfer of Dr. Eivazi. In the meantime, Dr. Eivazi returned to the University of Tuebingen with an Industry on Campus cooperation.
Dr. Alvise Barbieri
In southwest Germany the rivers, Ach and Lone have carved a spectacular landscape in which a number of cave sites have been repeatedly occupied by Neanderthals and later modern humans since their earliest arrival in Europe (ca. 43.000 years ago). From the excavation of these Prehistoric cave deposits archaeologists have discovered some of the oldest musical instruments and artworks in the world, which help illuminate the origins of art, music and religion. With a groundbreaking initiative, in January 2016 UNESCO has declared the Ach and Lone valleys, their cave sites, the deposits therein accumulated as well as the artifacts contained within them as a World Heritage Site. It is important to communicate to the public not only the significance of the earliest artworks but also the history of the landscape in which these spectacular findings have been conceived.
The aim of this proposal was to fund an innovative, temporary museum exhibition, called “Landscapes and Caves of the Latest Ice Age” which will guide the visitors to the discovery of the changes that took place in these two valleys during the period if the Latest Ice Age and how these changes have impacted the life of our prehistoric ancestors.
The exhibition was successfully designed and shown in the Prehistoric Museum Blaubeuren (UrMu) in the area for temporary exhibitions. Many interactive exhibits invited the visitors to discover and imparted interesting knowledge.
Dr. Thomas Kübler
"Look! Drive Safely"
In the Look! project, software was developed for robust measurement and reliable analysis of eye movements while driving. The algorithms used in the process open up eye movement data as a new source of information for machine learning and driver assistance systems which should help to make road traffic safer. As part of the project, eye-tracking glasses were developed which, together with a smartphone, represent a fully functional eye-tracking system (not just a recording system without any processing, as is the case with other products). The glasses feature light weight and extremely flexible connection for easy adjustment of the eye cameras. This makes them particularly easy to adjust to different people and, if necessary, they can look under glasses to avoid reflections. The software can also use the smartphone's sensor technology to associate gaze data with map position or driving maneuvers.
During the project, various events and training courses were attended during the project, and numerous contacts were established with companies. The project was further financed via a BMBF grant following the Innovation Grant funding. In the meantime, Dr. Kübler successfully founded his own company.
Dr. Rosi Bissinger
Since increased suicidal erythrocyte death (eryptosis) is a major cause of anemia in various diseases (including renal failure, sickle cell anemia, sepsis), it is imperative to therapeutically inhibit this increased eryptosis. As part of the Innovation Grant funding, Dr. Bissinger was able to identify three inhibitory substances each that are effective in renal failure and sickle cell anemia and one substance that showed moderate inhibition in sepsis. Furthermore, animal studies demonstrated anemia induced by increased eryptosis in proteinuric renal failure in a doxorubicin-induced mouse model. The Innovation Grant also identified additional diseases in which increased eryptosis occurs, including rheumatoid arthritis. The identified substances, which are effective in vitro against various diseases, could reduce or even prevent the increased eryptosis in the affected patients in a therapeutic approach. In order to continue and further finance the so far very successful and promising project, she received a consecutive funding for the following three years and a major player in the pharmaceutical industry showed interest in her results.
Dr. Fabian Vogt
In recent decades, the therapy and prognosis of some forms of cancer has improved significantly through the use of chimerized and humanized antibodies. However, the therapeutic success of such substances, especially in solid tumors, has been limited to date. To optimize antibody therapy of tumors, different strategies can be applied. One possibility is the development of bispecific antibody constructs. Bispecific antibodies have a target region acting against a tumor-associated antigen and an effector region to stimulate the T-cell receptor. Such a bispecific antibody was developed at the University of Tübingen using a newly generated PSMA antibody clone (10B3) to recruit T-cells via CD3. This bispecific antibody was optimized with respect to key features (off-target T-cell activation, serum half-life). With the help of the Innovation Grant funding, important and necessary questions (in vivo model, pharmacokinetics, serum half-life) were answered to be used for the approval of a planned clinical study I/IIa. Among other things, the cytokine profile resulting from the activation of T-cells by the bispecific antibody was characterized in more detail and an attempt was made to improve this in regard to side effects and a more effective design of the bispecific antibody. At the end of the grant, relevant research results were presented to the Paul-Ehrlich-Institute in the scope of a briefing book.
Dr. Julia Schmitt
The objective of the grant was the further development of preclinically evaluated radiopharmaceuticals for use in humans. After successful production and extensive quality assurance, a manufacturing license was sought from the regional council. At the same time, the GMP-compliant radiotracers were to be preclinically revalidated in the laboratories of the Werner Siemens Imaging Center. In addition, an extended toxicity study should be commissioned. In collaboration with the Center for Clinical Studies (ZKS) as well as the Center for Pediatric Clinical Studies (CPCS) of the University Hospital of Tübingen, a clinical phase I study on the use of the GD2 specific radioimmunoconjugates in patients was to be planned and prepared. Preclinical revalidation, GMP-like production and first imaging on patients was successfully implemented. However, due to large deviations of the emerging results from the previously collected data, the toxicity testing and consequently the application for a manufacturing license for the new tracer could not be started within the scope of the project.
Dr. Florian Karlewski
This project was dealing with the development of an instrument for the investigation of the spectral properties of lasers. The central element is an optical resonator. This allows the spectral properties of narrowband laser sources in particular to be measured with temporal resolution. This requirement is crucial for the development of new laser-based sensors and in the field of quantum technologies. In the first year of the project, a fully functional prototype including the associated measurement technology and software was built. This demonstrated the basic functionality with the targeted specifications. There was potential for optimization with regard to robustness against acoustic disturbances. In the second year of the project, this free-beam variant was optimized in many respects, especially the robustness against acoustic disturbances was improved, low-noise electronics and the compactness of the system were further developed. Finally, a prototype was completed, which provided the starting point for a product development by a company. In cooperation with the University’s Technology Transfer Office, the technology was licensed to a specialized laser company which hired Dr. Karlewski directly after the succesful Innovation Grant period ended.
Dr. Sascha Venturelli
The basis for the successful application for the Innovation Grant was the identification and characterization of the two hop constituents 6- and 8- prenylnaringenin (PN) as clinically interesting oncological agents and as immunostimulatory dietary supplements. Initially, the focus was on the production and evaluation of 6-PN and 8-PN nano-micelles to increase bioavailability, the testing of the active ingredients on primary tumor tissues, and the establishment of a dermatological formulation and preparation of a clinical trial. In the further course of the grant, the special emphasis was on the human study and the associated out-licensing as well as the acquisition of follow-up funding. The project received, besides several highly renowned publications, national and international attention, several prices, and resulted in two international patent applications.
Dr. Simon Lehle
DNA damage plays an important role in the development of many diseases, as well as in other bodily processes such as cell division, energy metabolism, and aging. Detecting DNA damage and repair of genomic lesions is crucial for better understanding the underlying relationships of many pathogenic developments.
The subject of this project was the so-called Long-Run DNA Damage Quantification (LORD-Q) assay, which allows the detection and precise quantification of DNA damage in human or mouse cells. This technique makes use of the real-time PCR method. While the original assay was developed for manual sample generation, processing and LORD-Q analysis, dialogue with collaborators and potential customers revealed that a high-throughput screening-capable version would be desirable. This led to the development of the Crude Cell Extract (CCE)-LORD-Q variant, in which the complex DNA isolation was replaced by lysis of the respective cell pellets and subsequent inactivation of the factors involved. The LORD-Q method was submitted for a German patent in December 2012. An international PCT subsequent application was filed in 2013. By means of the "DNA Damage and Repair Service Unit" of the University Hospital, the assay is made available in contract research for academic and industrial cooperation partners or customers, which has been active since January 2014.
Dr. Lehle has terminated the funding phase early, as he has taken up attractive positions in the biotechnology as well as the pharmaceutical industry.
Dr. Christina Schmalz
To ensure hygienic safety in indoor swimming pools, disinfection of the water with chlorine is essential. Chlorine can react with water constituents introduced into the system via the filling water or bathers to form undesirable and in some cases toxicologically relevant disinfection by-products such as trichloramine. Epidemiological studies show correlations of swimming pool attendance and risk of respiratory illness. Trichloramine, an unstable, irritant, volatile and typically swimming pool smelling compound is discussed as a cause. Therefore, it was proposed by the German Federal Environmental Agency to set limit values for this substance, thus necessitating easily applicable and reliable measurement methods to determine the concentration of tricholramine in indoor swimming pool air.
The aim of the project was to develop a simple, reliable and fast-responding measurement method for the quantitative and continuous analysis of air samples for trichloramine. For this purpose, ion mobility spectrometry was optimized as a sensor for field use and for online monitoring in indoor swimming pool air.
In parallel, an exchange took place with partners from industry such as a sensor company and a planning office for swimming pool and ventilation technology. In a follow-up project, the use of the sensor in continuous operation was to be tested in a swimming pool (with the aim of implementing energy-efficient, pollutant-related ventilation). Right after finishing the Innovation Grant project Dr. Schmalz transferred to the collaborating company.
Dr. Philipp Reautschnig
Site-directed RNA editing (SDRE) is a novel approach to treat disease by reprogramming genetic information at the RNA level. A major drawback of most SDRE systems is that they require two components: A guideRNA and an overexpressed artificial editing enzyme. The latter is known to cause massive global off-target events. During his PhD, Dr. Reautschnig developed a novel in-silico optimized design principle for guideRNAs that improved the recruitment of endogenous RNA editing enzyme ADAR by more than two orders of magnitude. Henceforward, this editing system required only the guideRNA component. Thanks to the funding by the Innovation Grant, Dr. Reautschnig was able to further advance this technology from that point onwards. Rules were developed for the design of optimal guideRNAs and these were tested in cell culture in editing both endogenous and disease-causing human transcripts. Functional restoration of mutant proteins has also been demonstrated in human primary cells. The multivalent nature of these guideRNAs resulted in very few off-target edits globally, as well as in target transcripts. In several rounds of optimization, a guideRNA was developed, which will prospectively find application in a murine disease model in the form of a viral vector. The work resulted in two patent applications and was published in Nature Biotechnology.
Dr. Martin Pflügler
Recently, exciting progress has been achieved in the treatment of cancer with strategies that mobilise T-cells against tumor cells: For example, bispecific antibodies that have a targeting part directed against a tumor-associated antigen and an effector part that stimulates the T-cell receptor (TCR)/CD3 complex on T cells can successfully activate these cells against tumors. In 2015, the prototype of this substance class, blinatumomab, was approved for the treatment of lymphatic leukaemias as part of a "breakthrough designation". However, bispecific antibodies can also cause considerable side effects through "off-target" activation of T cells, which prevent the application of optimal doses.
In his project, Martin Pflügler has transferred a novel format for bispecific antibodies to an FLT3xCD3 molecule, which can be used not only for the treatment of lymphatic but also myeloid leukemias. The bispecific format of the antibody offers an extended half-life compared to competing products and thus reduced manufacturing costs, as well as a more practical application for patients.
During the project, the bispecific antibody (CC-2) was optimised to such an extent that it is now suitable for use in humans. For clinical development, the molecule was out-licensed to an US venture fund (Cullinan Oncology) which started the clinical trial successfully in early 2022.
Dr. Nadine Anna Schilling
Pathogenic bacteria pose an increasing threat to human health, as many current antibiotics are no longer effective in fighting infections due to the development of resistance. The demand for new antibiotic structures is therefore enormous. In 2016, the discovery of lugdunin was published, which exhibits antimicrobial activity against numerous Gram-positive bacteria, including the multidrug-resistant "hospital germ" Staphylococcus aureus (MRSA). Lugdunin showed promising activity in initial mouse models, and no tendency to develop resistance has been observed in previous experiments. The Innovation Grant aimed to elucidate the commercial potential of lugdunin as a new lead structure for antibiotics. For this purpose, lugdunin and a more active synthetic derivative were tested in studies on solubility, stability, activity and toxicity, also within cooperations and collaborations with the Department of Microbiology, the University Hospital Tübingen, the University of Göttingen and external companies. Additionally, insight into the effect of lugdunin on artificial vesicles could be gained. The demand of the industry to modify Lugdunin in a way that it is water-soluble and additionally also active against gram-negative pathogens, could not be met within this grant.
Dr. Simon Drescher
The aim of the project was to examine change processes in companies from the perspective of modern rhetoric and to develop communicative strategies and procedures that foster innovation. Theoretical starting point were three approaches from modern rhetoric: The first approach came from fundamental rhetoric focusing on the question how the evocation of doubt enables people to accept new perspectives and opinions. The second approach derived from the studies of the persuasive potential of narratives since narratives often prove formative for culture and communication in organizations. Thirdly, methodological tools from conversation analysis were used to live-capture change processes and to understand the effectiveness of communicating strategies in organizations.
Starting from this rhetorical perspective, several change projects in two companies were initially accompanied through analysis and strategic guidance. These projects included the communicative roll-out of a new digital strategy and the analysis of the internal knowledge transfer between product development and sales.
Due to the disruptive influence of the Covid19 pandemic, innovation processes in the realm of digital work and digital leadership were reflected and strategies to cope with the new situation were developed for the cooperation partners. The projects dealt with topics of leadership over distance, digital way of working and mobile working policy.
In these areas formats to efficiently analyze needs and practically determine measures were developed. This analytical approach was followed by the development of strategic innovation formats for HR and organizational development to promote structures and individual skills for dealing with the disruptive potential of the new way of working.
The result of the project is a comprehensive transformation approach to sustainably develop leadership, work culture and innovation capability based on the specific cultural and organizational conditions of a company in each case. Part of this approach are analysis formats as well as adaptable and scalable development programs. Since the project was completed, this “Disruptive Rhetoric” approach has been implemented and systematically expanded successfully in development programs at other companies.
