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

Prof. Dr Gisa Gerold heads the PRESENt consortium. She is a biochemist and virologist. At the Research Center for Emerging Infections and Zoonoses (RIZ) of the University of Veterinary Medicine Hannover Foundation, her research group is working on novel proteomics approaches to shed light on the interaction of viruses with their host and to identify prognostic biomarkers. Within the consortium, she and her team are responsible for the purification and characterisation of noroviruses from patient samples. In particular, exosome-associated viruses are isolated and their protein content determined in cooperation with Prof. Lothar Jaensch (HZI, Braunschweig). In parallel, new organoid-based infection models are used together with Benjamin Heidrich (MHH) to test the effectiveness of disinfectants against noroviruses. Within the consortium, novel algorithms are also being developed to predict protein interactions.

"PRESENt integrates clinical, biological and Big Data research to advance our understanding of norovirus gastroenteritis and thus contribute to infection control."

Gerold Lab

Excellence Cluster RESIST

Collaborative Research Center 900

GeroldLab@Twitter

Wallenberg Center for Molecular Medicine (WCMM)

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.

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). 

Research Group Lothar Jänsch

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

Prof. Dr. Lothar Jänsch

Lothar Jänsch is the head of the research group “Cellular Proteomics” at the Helmholtz Centre for Infection Research. Together with the Technical University Braunschweig, he is appointed W2 professor for Proteome Research of Infectious Processes. His research focuses on translational projects in cooperation with academic, medical and industrial partners to discover novel mechanisms of immune cell activation to predict and control individual immune responses.

Dr. Marco van Ham

Marco van Ham is a senior scientist in the Jänsch Group. He is a cell biologist with a focus on cellular communication in and between immune cells. His main expertise are cell-cell contacts, microscopy-based immune monitoring (including laser-dissection microscopy) and in situ proteomics. Within the consortium, he is involved in the characterization of host-protein viral-protein interactions by mass spectrometry.

Peter L. Reichertz Institute for Medical Informatics

The Peter L. Reichertz Institute for Medical Informatics will take over the integration of clinical and OMICS data into the openEHR-based standard of the HiGHmed consortium in PRESENt. Furthermore, a focus is on the multimodal evaluation of the collected data. The linking of microbiome, proteome and clinical data using data-intensive technologies, such as machine learning, enables new insights into the pathomechanisms of norovirus infections. The interpretability of the results by physicians plays a special role in gaining knowledge. Therefore, various machine learning methods are used to analyse the clinical data, which, in contrast to "black box" methods, make it possible to understand which factors have influenced the result and to what extent. By means of the joint analysis of clinical and OMICS data through explainable machine learning, new insights into disease and progression are to be gained, which will enable a personalised prognosis and treatment of patients. For the analysis of the clinical data, the PLRI collaborates with the Groups Heidrich and Nejdl. The microbiological data are analysed in collaboration with Groups Strowig and Nejdl. An analysis of genetic markers for norovirus susceptibility is carried out jointly with Heidrich Group.

Prof. Dr. med. Dr. ing. Michael Marschollek

Prof. Dr. med. Dr.-Ing. Michael Marschollek is managing director and head of the Hannover site of the Peter L. Reichertz Institute for Medical Informatics at the TU Braunschweig and the Hannover Medical School. His research interests include Assistive Health Technologies (AGT), sensors, secondary use of clinical data, analysis of sensor data, data mining in medicine, prognostic models and sensor-enhanced information systems.

Dominic Wolff, MSc


Dominik Wolff is a research associate at the PLRI. His focus is on the use of data science methods and artificial intelligence in (bio-) medicine as well as the exploration of implicit knowledge. In PRESENt he is responsible for project coordination and planning within the PLRI.
 

Sarah Nee, MSc

Sarah Nee is a research associate at PLRI with research interests in bioinformatics and machine learning. She focuses on interpretable machine learning models and data integration and analysis of (bio)medical data.

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.

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


Publications

  1. A multitask transfer learning framework for the prediction of virus-human protein-protein interactions. Dong TN, Brogden G, Gerold G, Khosla M. BMC Bioinformatics. 2021 Nov 27;22(1):572. doi: 10.1186/s12859-021-04484-y. https://pubmed.ncbi.nlm.nih.gov/34837942/
     
  2. Personalized Prevention and Care of Severe Norovirus  Gastroenteritis (PRESENt). Graham Brogden, Franziska Woelfl, Dominik Wolff, Sarah Nee, Klaus-Hendrik Wolf, Ngan Thi Dong, Marco van Ham, Till-Robin  Lesker, Till Strowig, Lothar Jänsch, Megha Khosla, Wolfgang Nejdl, Michael Marschollek, Benjamin Heidrich, Gisa Gerold. German Society of Virology conference 2021, March 24th-26th, online.