Team:KU Leuven/Description

Project

HEKcite! Inspired by the human heart rhythm, we aim to create an electrophysiological oscillator from eukaryotic cells. Rhythmic contraction of heart cells is coordinated by a small group of cells located in the sinus node, which have an intrinsic frequency of de- and repolarization. This frequency of electrical oscillation is influenced by environmental parameters as well as certain molecular substrates. The oscillator that we aim to create consists of genetically modified excitable Human Embryonic Kidney (HEK) cells, altered to contain the intrinsic pacemaker ability found in sinus cells. As witnessed in heart cells, the rhythm would be dependent on substrate-activated ion channels in the membrane. As there is a great variety of ion channels available in nature, the oscillator could be modified to measure concentrations of many specific substrates. By integrating a certain ion channel into the oscillating system, specificity for a substrate can be chosen. Building an electrical oscillator from cells has several advantages. Intra- or extracellular changes that influence the conductance of ion channels in the membrane have an immediate impact on the frequency of oscillation. Once these cells are connected to each other (by for example gap-junctions), they generate an electrical signal that can easily be measured from a distance and non-invasively—similar to the way electrocardiography (ECG) and electroencephalography (EEG) measure electrical activity in the heart and brain. A multi-purpose sensor suitable for this system could be developed for medical and biotechnological applications. One such application is the measurement of drugs that interact with ion channels, such as antipsychotics, anti-epileptics or a certain class of immunosuppressants.

Professor Diethard Monbaliu MD, PhD

Professor Monbaliu is a reputable abdominal transplant surgeon, at the department of microbiology and immunology at UZ Leuven. He is also responsible for a course on topographical and radiological anatomy and supervises several thesis students.

Professor Monbaliu confirmed our suspicion that there is a need for a more dynamic measurement. In addition, he suspects that it could lead to a better evaluation of patients’ compliance. Together, these advances could result in fewer transplant rejections. He has also brought our attention to a novel and more prevalent immunosuppressant drug, tacrolimus. Finally, he mentioned that patient variability is an issue in his field, and that our device should take this into account. Want to learn more? Press for more details.

Before this meeting, we were investigating the immunosuppressant cyclosporine, as we thought this compound was commonly used after transplantations in order to reduce the chance of rejection. However, professor Monbaliu clarified that this is no longer the case. Instead, he brought our attention to the compound tacrolimus, which has taken cyclosporine’s place in transplantation medicine. Both drugs have the same mode of action, but tacrolimus has a better clinical outcome and less side effects. We were interested in using this novel drug for our research, but unfortunately, the compound is too expensive for us to use. Therefore, considering our financial situation and the input of the professor, we chose to use cyclosporine in our experiments.

Lastly, according to professor Monbaliu, a possible reduction of blood sampling could be a great advantage. However, he mentioned that every patient is different, which means that finding the optimal concentration of immunosuppressant for each patient could a challenge. As a result, our device should be calibrated individually for every patient. Together with professor Monbaliu, we suspect that the individual differences and the problems that go with them could be assessed during clinical studies. As soon as different patients and their different values can be assembled, it can lead to the procedures needed to determine the optimal drug concentration and calibrate our device.