Funding for collaborative research in personalised medicine

Acute myeloid leukaemia (AML) is a devastating disease, which inevitably causes death if left untreated. Over recent years, several genetic aberrations that drive or contribute to the development of leukaemia have been identified and linked to the prognosis of an leukaemia outbreak in patients. However, using increasingly sensitive diagnostic tools revealed a large heterogeneity in the molecular landscape of AML which compromises the predictive value of individual genetic alterations. As also reported for other malignant diseases, AML often consists of heterogeneous subpopulations of cells harbouring different genomic aberration. It is due to this diversity that the treatment of leukaemia fails and relapses, since clonal subpopulations of cells may resist treatment which may lead to disease progress or relapse. Effective treatment should thus either target all subpopulations, or evolve with the tumour to adapt as new clones become dominant. In order to develop individualised therapies for leukaemia-patients it is hence key to link the genetic make-up to progression models and clinical outcome. 
This research project co-led by Jack Kuipers from the Computational Biology Group of Niko Beerenwinkel together with clinician Claudia Lengerke from the University Hospital Basel aims to discover how mutational interactions affect the outcome of patients undergoing stem cell transplants, and how the analysis of genetic sequencing data can contribute to the prediction of tumour progression and of the patient’s response to specific therapies. The project combines statistical modelling with the assessment of the treatment response in a pre-clinical animal model before translating the findings to human patients. The project aims to establish an analysis tool based on genetic sequencing data that may help clinicians to personalise the treatment in AML and improve the success rate in patients suffering from leukaemia.

The second project receiving funding from the Basel Personal Medicine Initiative focuses on the neurons that produce the neurotransmitter dopamine and their role in one of the most prominent human neurological disorders, Parkinson’s disease. Dopaminergic neurons are the main source of dopamine in the mammalian central nervous system and their loss is associated with the progression of Parkinson’s disease. How do dopaminergic neurons function, how do they communicate with one another and how can their healthy status be preserved? In order to model some aspects of Parkinson’s disease in the lab, dopaminergic neurons will be derived from human stem cells. Manuel Schröter from the Bio Engineering Laboratory of Andreas Hierlemann will then use recording devices, so-called microelectrode arrays, to probe the electrical activity of these nerve cells. This will help to understand the functioning of dopaminergic neurons and their role in neuronal networks. In a second step, Schröter and his collaborator Professor Verdon Taylor from the University of Basel (Department of Biomedicine) will use diseased cells similar to those found in patients suffering from Parkinson’s disease. The researchers will then test different drugs that could potentially rescue the functioning of dopaminergic neurons. This study will improve our understanding of neuronal physiology in Parkinson’s disease and provide valuable information for the development of personalised therapies for this severe neurological disorder.