At some point in our lives, we will all be affected by one or more common complex diseases, such as cancer, cardiovascular pathologies (heart attacks, strokes), diabetes, chronic inflammatory diseases (e.g. rheumatoid arthritis, Crohn's disease) or neurological diseases (Alzheimer's disease). The rising incidence of these common pathologies is linked to our lifestyle, but also to the ageing of our population. The economic burden attributable to these pathologies is rapidly becoming unsustainable, putting our social security system at risk. There is an urgent need to adapt the management of these pathologies, and it is generally accepted that P3 (Preventive, Personalized, Precision) medicine will play an essential role in this.
ENSEMBLE's objective is to initiate the deployment of P3 medicine in the Walloon Region. ENSEMBLE will be able to get off the ground thanks to initial ERDF funding from the MEDRESYST portfolio. ENSEMBLE comprises five actions:
- A Walloon contribution to the European "1M Genomes" project by sequencing the genomes of Walloon citizens representing the region's ethnic diversity. The sequencing will be carried out by the GIGA genomics platform.
- Clinical deployment of "Polygenic Risk Scores" (PRS) for "common complex pathologies" including breast cancer, colon cancer, chronic inflammatory bowel disease, diabetes and myocardial infarction. The AI models used will be developed on the basis of UK Biobank and public GWAS data. They will be gauged and calibrated by genotyping corresponding local case-control cohorts (200 individuals per pathology). Genotyping will be carried out at the GIGA genomics platform. PRS will be calculated under the supervision of Professors Geurts, Bours and Georges.
- Establishment of a Walloon "learning" cohort (under the supervision of Prof. Edouard Louis and Dr. Sophie Vieujean). In order to eventually generate more accurate and informative PRS (local population, ethnic diversity, richer clinomic data), we will collect biological samples from at least 10,000 Walloon citizens visiting Liège University Hospital. DNA will be extracted from these samples and stored in the Biobanque Hospitalo-Universitaire de Liège (BHUL).
- Establishment of clinomic records for the calculation of PRS by automated AI extraction of structured data from CHU's electronic medical records. This project is led by Professor Kolh.
- The search for rare disease determinants by sequencing the genomes of newborns with severe syndromes and their parents ("trios"). This project is under the direction of Professor Vincent Bours.
Budget : €1,723,795
React-EU supplements - Strengthening innovation in healthcare
BIOMED Technology Support React-EU
On May 6, 2021, the Walloon government decided to grant a budget supplement to the Technology Support project in the Biomed Hub portfolio, as part of the REACT-EU initiative. The purpose of this supplement is to extend the staff essential to the smooth running of the technology platforms until the end of 2023. In addition, the platforms wish to complete and/or upgrade current equipment in order to remain at the cutting edge of technology, maintain high-performance research and envisage new applications in line with market developments.
This is an extension of the PREDIMID project, which focuses on chronic inflammatory bowel disease (IBD).
PREDIMID - Development of diagnosis and prognosis tests for Inflammatory bowel disease patient follow-up, especially for Crohn disease: Identification of biomarkers and their validation by SRM (Selected Reaction Monitoring)
The PREDIMID project concerns the identification of biomarkers by proteomics in the context of Inflammatory Bowel Disease (IBD). Crohn disease (CD) and Ulcerative colitis (UC) are both IBD and these patients show lesions within the digestive tract that can severely impact quality of life. The incidences of CD and UC are respectively 10/100000 and 6/100000 per year; whereas IBD prevalence is 0.3% in EU. Life expectancy of IBD patients is close to the one of the general population. A first unmet clinical need for IBD patients concerns lesion diagnosis and stratification of patients according to location and type of lesions. A second issue is the prediction of relapse when the patients are in remission induced by a treatment with biologics (particularly anti-TNF Antibody). Only colonoscopy (invasive, not comfortable and costly) is used as a gold standard to evaluate the presence and severity of lesions or to control for mucosal healing. It has been shown that deep mucosal healing was associated to a lower relapse risk in CD. Beside endoscopy the best marker of relapse in faecal calprotectin which is also a surrogate marker for mucosal healing.
In this context, PREDIMID is a research project involving prospective IBD patients’ enrolment and collection of samples. Proteomic analyses are planned to identify and confirm some potential biomarkers highlighted at the tissue level and at the systemic level (in blood).
Currently, we collect different types of samples: blood-derived products, stools and tissue biopsies, thanks to the clinical activity of Professor Edouard LOUIS (head of PREDIMID) and his colleagues at the University Hospital of Liège, CHU Liège.
We have identified two sets of candidate biomarkers linked to the relapse risk and associated to the patient lesion status by studying CD ulcer, the most frequent CD lesion. The refinement of the two sets of candidate markers and a specific method of quantification are under progress to confirm these biomarkers in blood. Our data should be consolidated thank to the analysis of a second cohort of samples that will be originated from the SPARE clinical trial initiated through the European consortium named BIOCYCLE, project H2020 (https://biocycle-project.eu/).
This validation of markers is mandatory for any commercial development that could be transposed and used in clinics as a companion diagnosis/ prognosis test. Such test could be proposed as an alternative to colonoscopy for IBD patients, if showing the same statistical power and at lower cost. Such laboratory test would have an important impact on the comfort and safety of clinical IBD patient management, on health care related costs and for a company that would develop such a companion test.
AMD - New therapeutic targets for age-related macular degeneration
Age-related macular degeneration (AMD) is the leading cause of blindness in people over 50 in developed countries. Current treatments only help to stabilize the disease. Additionally, resistance to these treatments appears inevitably leading to the irreversible loss of vision. It is therefore crucial to identify new therapeutic targets and develop tools to block them. We have identified a new potential therapeutic target whose expression has been correlated with increased neovascularization typical of AMD. Antibodies blocking this target have been produced in close collaboration with the biotechnology department of the CER group. Two types of antibodies have been produced: Single Chain Fragment Variable (scFv) generated by phage display technique and IgG antibodies produced by mouse immunization. Antibodies are selected through activity tests and in vitro functional assays. In order to test their therapeutic efficacy in a preclinical model, a new equipment adapted to rodents has been acquired and calibrated to induce the laser choroidal neovascularization accurately and reproducibly.
KIT QUANTA - Absolute quantification of proteins in complex matrices (blood, urine and cerebrospinal fluid or CSF) thanks to a “universal” standardization kit
In the world of biomarker discovery, there are few validations of biomarker candidates. The discovery and validation steps in the development of biomarkers remain quite challenging and lengthy. The need for high-throughput technique is therefore urgent. SRM method (Selected Reaction Monitoring) can solve the problem in offering high-throughput analyses. The difficulty of this method lies in the implementation of standardization for absolute quantification. Different standardization approaches now exist in proteomics but all have their limitations. One example is the use of isotopically-labelled peptides for the absolute quantification of proteins. This method is highly specific of the protein to quantify but does not take into account all the bias introduced at each step of the process needed before SRM analyses. In combination with this already well-known technique, our “kit” will allow to control the whole preparation process and therefore will be a useful and necessary tool for longitudinal studies or studies involving a large number of samples in the process of biomarker discovery or validation. Several actors work in collaboration to reach this goal: the Mass Spectrometry Laboratory (MSLab) in ULiège, the laboratory of Proteomics and Microbiology (ProtMic) in UMons and Eurogentec S.A.
Contact Mass Spectrometry Laboratory - France Baumans
BIODEC aims at developing innovative, eco-friendly and sustainable coatings capable of degrading indoor air pollutants via the use of natural macromolecules. These coatings are produced by aqueous or liquid phase deposition processes on existing structural elements of our enclosed living spaces. They can be applied to a wide range of surfaces (metal, plastic, glass, etc.).
Contact Laboratory of Molecular Biomimetic - Patricia Lassaux
In addition to these research projects, the ERDF finances BIOMED TECHNOLOGY SUPPORT
Thanks to quality research and cutting-edge technologies, the GIGA-CRC cluster already constitutes an ecosystem which has made it possible to attract companies (since 2008, almost 40 companies on the giga site alone) and / or to amplify collaborations with companies in the sector. This cross-fertilization between academic and private sector actors is essential for the economic redeployment of the region, but requires maintaining infrastructure, equipment and expertise at the highest level, which will be made possible thanks to this project.
The technological platforms, which bring together advanced technologies and high-level skills, are accessible to researchers from ALL sectors: academia, SMEs, large companies, job seekers or employees in training supervised via the GIGA-FOREM training center. The platforms therefore clearly respond to the concept of EXCEPTIONAL TECHNOLOGICAL EQUIPMENT defined by the Walloon Region and to the definition of RESEARCH INFRASTRUCTURE seen by Europe in the Horizon 2020 program. In order to remain at the forefront of innovation, to take up the challenges proposed by companies (both technological, in terms of quality standard and speed of execution), to further improve the services rendered to researchers and finally, to ensure that they are in adequate infrastructure, it is essential: (1) to COMPLETE or UPGRADE existing equipment; (2) to provide the EXPERTISE required for the provision of services on this advanced equipment.