Mitochondria is the power-generating part of a cell, and it seems that in Parkinson’s disease (PD), mutations in the mitochondria of the cells that produce dopamine (called neurons) cause the energy supply to be cut off. The result is that the neurons die, dopamine production is interrupted, and the symptoms of PD appear.
The researchers in PD-MitoQUANT think that studying this dysfunction could lead to new targets for PD drugs. The team includes the SME geneXplain, whose customers are researchers who need to understand the processes of gene regulation (genes turning on and off) in different biological processes, in the study of everything from cancer to fish evolution. GeneXplain researchers Dr. Olga Kel-Margoulis, Kamilya Altynbekova and Dr. Alexander Kel explain their involvement in the project.
What is geneXplain’s contribution to the project’s quest to find new drug targets for PD?
We specialise in reconstructing molecular mechanisms of complex diseases and Parkinson’s Disease is a very good example of such intricate pathology. We are applying our bioinformatics tools to analyse various ‘-omics’ data generated in the consortium and trying to reconstruct causative mechanisms happening in these cells and explain how molecular pathways are pathologically altered, with our attention focused on those pathways that may lead to, or can be triggered by, mitochondrial dysfunction.
As a result of such analysis, we reveal master regulators, which are genes and their encoded proteins that play a key role in such altered pathways. These master-regulators are proposed as promising drug targets in PD. We hypothesise that inhibiting such master-regulators may prevent the pathological alteration of the pathways involved and restore the normal processes in the neurons.
What kind of data have you gathered so far?
We have collected in our databases detailed information about 700 molecular biomarkers related to PD, including causative, correlative, and preventive biomarkers, as well as biomarkers involved in the mechanism of the disease initiation and progression.
Among these biomarkers there are 47 transcription factors that play an important role in the regulation of expression of these PD-related genes. These genes are involved in more than 150 signalling and metabolic pathways. All this knowledge allows us to infer new relationships between genes and proteins involved in PD pathology and our analysis leads to discovery of novel connections in the disease altered pathways.
Analysis of such disease altered pathways is absolutely necessary for reaching the goals of the project since such alterations cannot be identified by standard tools.
Can you tell us more about your bioinformatics tools?
Our algorithms help us to come closer to the actual molecular mechanism of the disease, making our prospective drug targets and treatment predictions much more accurate and reliable. Our computational platform, called ‘geneXplain platform’ currently includes more than 200 different bioinformatics and systems biology tools and about 100 complex pipelines. Many of these tools will help us to achieve the goals of the project.
Our aim is to constantly improve our software solutions and databases in order to provide our customers with the best of what’s possible in intracellular modelling of the studied pathology. We are actually coming to the point when not only researchers, but also medical doctors are becoming interested in such solutions. We have started to attract the attention of doctors in the fields of complex diseases such as oncology, neurodegenerative and autoimmune diseases and our new product, Genome Enhancer will soon allow doctors to use treatment suggestions produced by our precision medicine tool, using artificial intelligence to reconstruct molecular mechanism of the disease for a group of patients or for one specific patient.
This phenomenon is explained by the greater involvement of medical doctors in the studies of the diseases’ molecular mechanisms, due to targeted therapies and increasing availability of omics technologies in the clinics. We are almost sure that one day it will be not only the researchers who will be asking us about the details on the improvement of our tools, but also the medical doctors too.
In what ways is the partnership in IMI a benefit to your company?
Any big research project, uniting the best competences in a certain field, always gives an incredible ability to learn more, expand your current view on the studied problem, meet new colleagues and get inspired by their ideas and plans towards improvement of the currently available technologies. The value of IMI partnership is hard to overestimate – the project indeed gives basically unrestricted abilities to apply newly developed technologies in the clinical trials, helping the innovative approaches reach the general medical practice in a faster and safer way.
PD-MitoQUANT is supported by the Innovative Medicines Initiative, a partnership between the European Union and the European pharmaceutical industry.