Ghent University: Ghent University researchers win ERC Consolidator Grant

The winning projects
MICROBE: the interplay between ‘us’ and ‘them’
Our bodies are home to trillions of bacteria and the interplay between “us” and “them” determines the development and course of infectious diseases, chronic diseases such as inflammatory bowel disease, as well as the response of tumors to cancer therapy. For this interplay, bacteria use, among other things, various messenger substances packed in tiny bubbles (also called vesicles) that they release. Although this phenomenon has been described long ago, its biological significance in the interplay between “us” and “them” is largely unknown until today. The reason for this is that innovative techniques are necessary to study these bacterial vesicles in body fluids.

An Hendrix’s research group has played a pioneering role in the development of these techniques, resulting in the first identification of bacterial vesicles in the blood of patients with inflammatory bowel disease, HIV and cancer. These findings resulted in the conceptualization of the ERC consolidator project MICROBE. An Hendrix and her research team will map bacterial vesicles in body fluids and investigate how these vesicles influence the disease course of patients. These insights can contribute to the development of diagnostic applications that allow to monitor the interplay between “them” and “we”, and, to therapeutic applications that adjust the balance between “them” and “we” and thus guarantee health.

EpiGuide: detecting therapy resistance in cancer patients
The aim of EpiGuide, the project of Katleen De Preter, is to develop a blood test that allows in-time detection of therapy response in cancer patients under treatment. The past decade important progress has been made in cancer treatment with the introduction of more personalized approaches. However, an important cause of death remains the development of therapy resistance by the cancer cells. Hereby, changes occur in cancer cells so that they become insensitive to the treatment. In addition to changes in DNA of the cancer cell, changes in the epigenetic code (chemical structures of the DNA code) are an important cause of cancer cell plasticity and development of therapy resistance. Nowadays, research is focused on the understanding of epigenetic mechanisms leading to resistance, however efficient methods that allow to detect and follow up on epigenetic changes of cancer cells under treatment do not exist.

With the EpiGuide project, Katleen De Preter aims to develop a minimal invasive test that detects the epigenetic changes by analysing circulating tumor DNA in the blood. To this end, both analytical and computational methods will be optimized that will first be validated in blood samples of cancer mouse models after which it will be tested in blood samples of cancer patients. This study will focus on two cancer entities, i.e. a rare childhood cancer (neuroblastoma) and a frequent cancer in women (breast cancer), but the approach will be applicable in other entities as well. The clinical application of the EpiGuide test will allow the adaptation of treatment regimens from the first signs of therapy resistance. In addition, it will help in the improved understanding of epigenetic resistance mechanisms.

‘IMPACTUM’: assessing the impact of urgent measures in protecting at-risk detainees in Latin-America
Urgent Measures (UMs) are granted by international human rights bodies to protect persons who are in a situation of extreme gravity and urgency. In Latin America, UMs are mostly granted to protect detainees, when their right to life, integrity and/or health are in danger of being violated. When a UM is granted by a human rights body, the State is requested to provide detainees with immediate access to medical care, drinking water, food, sanitation, fresh air, or natural light. In such cases, UMs may prompt emergency protective actions that can, in the most extreme circumstances, save the life of the beneficiary of these measures. Though UMs have been issued on thousands of occasions, they have attracted little academic attention. The few studies that exist focus on a doctrinal analysis on compliance. Such studies have several shortcomings in that they primarily examine only procedural legal aspects, and often excessively rely on information provided by human rights bodies themselves. As UMs often face practical, financial and political constraints that shape and limit their implementation, it is crucial to establish a better understanding of how these measures are applied in practice.

IMPACTUM, written by Clara Burbano Herrera, is an ambitious research project that moves beyond the traditional legal research questions and methods of analysing UMs. It instead proposes an interdisciplinary study of UMs that: 1) considers the context in which UMs are enforced and how they are applied on the ground; 2) assesses the impacts of UMs on detainees, legal and institutional systems and on (inter)national actors; 3) discusses their strengths and limitations; and 4) analyses their wider learning effects. With reference to UMs granted by 4 human rights bodies to protect at-risk detainees in 6 Latin American countries, IMPACTUM will develop a critical normative impact framework useful to provide a deeper theoretical analysis, as well as insight into how to formulate UMs to maximise their practical protective effects. IMPACTUM will thus uncover and present new knowledge on emerging issues with UMs that are currently unaddressed in academia and in practice.

AMICAS: an Adaptive Multi-drug Infusion Control system for general Anesthesia in major Surgery
The project of Clara-Mihaela Ionescu, AMICAS, proposes an Adaptive Multi-drug Infusion Control system for general Anesthesia in major Surgery. A major challenge in anesthesia is to adapt the drug infusion rates from observed patient response to surgical actions. The patient models are based on nominal population characteristic response and lack specific surgical effects. In major surgery (for instance, cardiac, transplant, bariatric surgery) modelling uncertainty arises from significant blood losses, anomalous drug diffusion, drug effect synergy/antagonism, anesthetic-hemodynamic interactions, etc. This complex interplay requires superhuman abilities of the anesthesiologist, acquired along many years of training and practice. How can we mimic this large amount of expertise? And provide support for their critical decisions?

Computer controlled anesthesia holds the answer to be the game changer for best surgery outcomes. Although few, clinical studies report that computer-based anesthesia for one or two drugs outperforms manual management. In reality, clinical practice performs a multi-drug optimization problem while mitigating large patient model uncertainty. The anesthesiologist makes decisions based on future surgeon actions and expected patient response. This is a predictive control strategy, a mature methodology in systems and control engineering with great potential to induce faster recovery times and lower the risk of post-surgery complications.

The interdisciplinary team of AMICAS aims to advance the scope and clinical use of computer based constrained optimization of multi-drug infusion rates for anesthesia with strong effects on hemodynamics. In doing so, we identify multivariable models and minimize the large uncertainties in patient response. With adaptation mechanisms from nominal to individual patient models, we design multivariable optimal predictive control methodologies to manage strongly coupled dynamics occurring in patient’s vital signs during major surgery. Ultimately, to maximize the performance of the closed loop, we model the surgical stimulus as a known disturbance signal and additional bolus infusions from anesthesiologist as known inputs.

The AMICAS project integrates human expertise with computer optimization to create a successful solution for breakthrough into clinical practice.

Comments are closed.