Genetic plasticity – How do human embryos cope with aneuploid cells?

Dr. ir. H. Marks, Radboud University
Dr. E. Coonen, Maastricht University Medical Center+
Dr. ir. S. Giselbrecht, Maastricht University

Aneuploidy, the presence of an abnormal number of chromosomes in a cell, is highly prevalent in human embryos derived by in vitro fertilization (IVF). It is a major cause of early pregnancy loss. Preimplantation genetic testing for aneuploidy (PGT-A) has therefore been introduced into IVF clinical practice to exclude aneuploid embryos from transfer. However, there is growing evidence that preimplantation embryos of mixed ploidy, so-called mosaic embryos, can result in healthy babies born, questioning PGTA efficacy. Here, we bring together an interdisciplinary, ambitious team of researchers that will use new, powerful embryo models to study how human embryos cope with aneuploid cells. Our discoveries will provide insight into how early human embryo develop and will help the decision-making process of clinical embryologists when choosing between embryos of varying aneuploid signatures for transfer to the uterus.

No transmission, no malaria: dissecting gametocyte biology of vivax-type malaria parasites

Dr. R.C. Bartfai,  Radboud University
Dr. C.H.M. Kocken, Biomedical Primate Research Center

Malaria is a deadly infectious disease that is claiming millions of life’s in the tropics and due to global warming might start infecting people in Europe again. It is caused by parasites, which can spread from patient to patient via mosquitos. While the sexual stage of the parasite (gametocyte) that can be spread by mosquitos could be good target for intervention, we know very little about this stage. In this project, we will use advanced molecular technologies to understand how gametocytes of different malaria parasites are forming. The knowledge and tools generated in this project will be invaluable for the development of new ways to control and eliminate this deadly disease.

Prevention of pelvic floor trauma after childbirth

Dr. Z.G. Guler, Amsterdam UMC AMC
Dr. P.K. Kouwer, Radboud University
Prof. dr. C.V. Verhoeven, VUMC

Pelvic floor disorders (PFDs) affect millions of women globally and represent a major public health. During vaginal birth, (over)extension causes rupture of the musculature and connective tissue, resulting in pelvic floor damage. We hypothesize that impaired healing and incomplete recovery after the trauma in the pelvic tissues caused by childbirth contribute to the PFD symptoms. We suggest a preventive strategy to minimize the extent of damage and enhance tissue healing after birth. In this project, we will develop an injectable hydrogel to apply into the damaged tissue to improve healing and therefore to prevent PDFs. This project presents a proof-of-concept and innovative approach to prevent PDFs. This project is the first step for the clinical application of hydrogel that will result in improved quality of health among young mothers worldwide.

Don’t hit the avatar? Development and pharmacological validation of a novel transdiagnostic RDoCbased model on reactive aggression

Prof. A. Blokland, Maastricht University
Dr. J. Lobbestael, Maastricht University 
Dr. R. Schreiber, Maastricht University 
Prof. dr. R.J. Verkes, Radboud University  

Aggression is a major concern in mental health settings across a wide range of disorders, with devastating effects on patients, victims, and health care workers. Despite this large societal impact, causes of aggression are still incompletely understood and therapeutic solutions are poor. This project aims to improve this situation in 3 consecutive projects. First, we will conceptualize the nature of aggression by applying the Research Domain Criteria approach. Second, we will develop a test-battery measuring the distinct steps (threat, thinking errors, disinhibition) leading to aggression measured in Virtual Reality. This will enable identifying distinct ‘biotypes’, further validated by testing the effects of two drugs. Finally, we will assess how the two drugs reduce aggression in two patient groups. Our multidisciplinary team enables us to approach aggression integratively, with the ultimate objective to provide an individualized pharmacological intervention to lower aggression.