Paving the way towards personalized PREvention and care of SEvere Norovirus gasTroenteritis

 

“PRESENt integrates clinical, biological and big data research to advance our understanding of norovirus gastroenteritis ultimately impacting infection control”

Our research focus within PRESENt is the elucidation of norovirus associated host proteins and testing of disinfectants to prevent norovirus infection. The long-term aim is together with the PRESENt partners to identify prognostic markers of severe disease and improve preventive disinfection strategies.
In pursuing this research project, we build on our long-standing expertise in high resolution proteomics and our collaboration partners’ expertise in organoid models of gastrointestinal disease.
Collaborating groups: Prof. Dr. Thomas F. Schulz (Medizinische Hochschule Hannover, Institute of Virology für Virologie), Prof. Dr. Nihal Altan-Bonnet (NIH, Bethesda, USA), Prof. Dr. Lennart Svensson (Linköping University Sweden)

Speaker of the consortium PRESENt

Prof. Dr. Gisa Gerold

Postdoctoral Researcher

Dr. Graham Brogden

Graham Brogden joined the consortium as a postdoctoral researcher at the start of 2020. His main research goal is to elucidate norovirus protein-host protein interactions to help identify prognostic biomarkers that can explain the difference between acute and mild symptoms. To identify these biomarkers, norovirus containing exosomes will be isolated from patient samples and used to infect intestinal organoid cultures. The method used for the isolation of exosomes from stool samples was developed by our collaborating partner, Prof. Dr. Nihal Altan-Bonnet (NIH, Bethesda, USA) whose lab was visited by Graham Brogden during February 2020. Host protein-viral protein interactions will be subsequently determined by a PRESENt consortium partner, Prof. Lothar Jaensch (HZI, Braunschweig) using mass spectrometry and further analysed by two additional consortium groups (Prof. Wolfgang Nejdl, L3S, Hannover and Prof. Michael Marschollek, MHH, Hannover) using bioinformatics.

Research Group Lothar Jänsch

Prof. Dr. Lothar Jänsch

Dr. Marco van Ham

The main focus of the Jänsch group within the consortium is the elucidation of specific host factors associated with infectious shed norovirus particles. The presence of norovirus-specific exosomes in the stool of patients and the notion that the content of exosomes differs highly between individuals depending on the host immunity, makes these exosomes good candidates for the characterization of predictive markers. To identify these biomarkers, norovirus-containing exosomes are isolated from patient samples (with Prof. Gisa Gerold, TiHo, Hannover) and are subsequently analysed by using shotgun proteomics. In this particular project, we make use of a state of the art high-resolution liquid chromatography – mass spectrometry instrument combination designed for clinical sample acquisition (Evosep One & timsTOFPro from Bruker). Data analyses and biomarker validation will be supported by the groups from Prof. Wolfgang Nejdl (L3S, Hannover) and Prof. Michael Marschollek (MHH, Hannover). Our general hypothesis is that the composition of norovirus-associated exosomes varies between individuals and that proteomic analyses will reveal signatures for acute and mild versus severe and chronic infections.
www.helmholtz-hzi.de/cpro

Deputy Spokesman of the consortiums PRESENt

PD Dr. med. Benjamin Heidrich


Benjamin Heidrich is a physician specialized in internal medicine. Within the consortium he and his team are responsible for the data collection and data analysis of patients with proven Norovirus infection in the last 10 years. Furthermore, his team is organizing the recruitment of patients for the prospective study as well as the sample collection which is the ground for many of the other planned projects within the consortium. He is co-coordinator in the TTU GI Infection within the German Center for Infection Research for the partner site Hannover-Braunschweig and the head of the Centre for Gastrointestinal Clinical Trials (CEGICLIN) within the TTU. Beside Norovirus infection his research focus lies on the role of microbiota in gastrointestinal and hepatological diseases. 


Further information can be found here: 

CEGICLIN: Centre for Gastrointestinal Clinical Trials (CEGICLIN) | German Center for Infection Research (dzif.de)

TTU GI Infection: Gastrointestinal Infections | German Center for Infection Research (dzif.de)

MHH: Medizinische Hochschule Hannover : AG Heidrich (mhh.de)

RESIST: Project B11 – RESIST (resist-cluster.de)

Doctoral Researcher

Franziska Wölfl

Franziska Wölfl joined the consortium as a doctoral researcher in the group of PD Dr. Benjamin Heidrich at the start of 2020. Her focus is on the translational aspect of the PRESENt consortium and thus, she wants to determine early onset clinical biomarkers to distinguish between mild and severe cases of Norovirus. Furthermore she works with intestinal organoid cultures in collaboration with Prof. Dr. Guntram Graßl (Medizinische Hochschule Hannover, Institut für Mikrobiologie). These organoids are used to determine the efficacy of different disinfectants on Norovirus. They will be used to verify potential genetic markers for Norovirus susceptibility in vitro after initial in silico discovery by Prof. Michael Marschollek (Medizinische Hochschule Hannover). 

Dominic Wolff, MSc

Dominik Wolff is responsible for project coordination and planning within the Peter L. Reichertz Institute for Medical Informatics (PLRI) and was involved in the application process. On the one hand, an openEHR data platform for the integration of clinical and OMICS data is developed at the PLRI in PRESENt. Furthermore, a focus is on the multimodal analysis of the collected data. Linking microbiome, proteome and clinical data by data intensive technologies, such as machine learning, enables deep insights into the pathomechanisms of norovirus infections. To generate insights, the interpretability of the results by clinicians plays a special role. Close collaboration within the consortium is an integral component of PRESENt.

Sarah Nee, MSc

At the Peter L. Reichertz Institute for Medical Informatics (PLRI), Sarah Nee is responsible for the integration of the data into an openEHR data platform, and is involved in the analysis of the clinical and OMICS data, in particular the microbiome. Especially in a clinical context, it is important that scientists and users are able to understand how machine learning applications have produced their results. Therefore, to analyze the clinical data, different machine learning methods will be employed where as opposed to „black-box“ concepts, the influence of the different input features on the result can be inspected. By jointly analyzing the clinical and OMICS data with explainable machine learning new insights on disease and progression are to be provided that allow for a persoanlized prognosis and care of the patients.

Research Group Wolfgang Nejdl

The main focus of the Nejdl group within the consortium is on developing machine learning approaches for joint learning from environmental, individual patient and –OMICs data to predict severe gastroenteritis and possible points of intervention. The overall hypothesis is that no single data type can reveal completely the complexities of the underlying disease. Joint learning from multiple heterogeneous data would compensate for missing or unreliable information in any single data type. Moreover, several sources of information pointing to the same outcome can increase the overall confidence of prediction. Within the consortium the group collaborates with Gerold’s group for analysing norovirus-human protein interactions.  For analysing clinical data the group will collaborate with groups from Heidrich and Marschollek. For analysing microbiomic data the group will collaborate with groups from Strowig and Marschollek.

More Information about the team members

Prof. Dr. techn. Wolfgang Nejdl

Prof. Dr. technical Wolfgang Nejdl is the director of the L3S research center and heads the data analysis team of PRESENt. His research interests include information retrieval, data mining, data science, semantic web and precision medicine.

Webpage: https://www.kbs.uni-hannover.de/~nejdl/

Dr. Megha Khosla

Dr. Megha Khosla is a senior researcher at L3S and focusses on developing machine learning algorithms for graph structured data and precision medicine. She is also responsible for supervising and coordinating L3S’ activities in PRESENt.

Webpage: http://www.l3s.de/~khosla/

Ngan Thi Dong

Ngan Thi Dong is a PhD student at L3S with research interests in deep learning and precision medicine. In PRESENt she focusses on developing deep learning tools/techniques to learn from heterogenous medical data.

Contact

Prof. Dr. Gisa Gerold

Head of the Research Group "Molecular and Clinical Infectiology"
University of Veterinary Hannover (TiHo)

phone:
0511 953-8781
write an e-mail