SBW2016

Richard Bonneau

Associate Professor of Biology, Computer Science; Faculty Director of Bioinformatics, New York University
Bonneau Lab

Talk title: New methods for learning large network models underlying immune-microbiome interactions

In the presentation Richard will discuss their efforts to model diverse immune cell type’s interactions with their environment and with the microbiome. The first part of the talk will detail new efforts to learn large scale biophysically motivated network models of both rare and common immune cell types. This inference results in both network models and estimates of regulatory factor activity in a host of conditions. The second part of the talk will consider new methods for learning microbial interaction networks (from both environmental and human associated datasets) and recent efforts to both learn these networks and also use the networks to model connections to complex meta-data (such as host immune factors, genetics and metabolites) as well as new methods for making sense of microbiome time series. The talk will finish with some discussion of limitations and implications for experimental design (alas, most questions posed during the talk will go unanswered).

Ron van Schaik

Professor of Pharmacogenetics, Department of Clinical Chemistry, Erasmus University Medical Center, Rotterdam, The Netherlands

Ron is Director of the International Reference Center for Pharmacogenetics and leads the Unit for Research & Development at the department of Clinical Chemistry. Many drugs that are currently available are of the type “one size fits all”, but they don't work the same way for everyone. Pharmacogenetics is the study of how genes affect a person’s response to drugs. Ron´s research focuses on clinical implementation of pharmacogenetics, with the main interest directed towards pharmaceuticals used against transplantation/immunosuppression, oncology, pain, psychiatry, HIV and anticoagulation. Pharmacogenetics is still in its infancy and currently the implementations are (unfortunately) quite limited. In the future, pharmacogenetics will allow for the development of tailored treatments against a wide range of health problems.

Talk title: Clinical Implementation of Pharmacogenetics: Do YOU have your DNA passport?

Talk Abstract: Interindividual variation in drug metabolism is a factor affecting successful drug therapy. Adverse drug reactions are responsible for 5-7% of hospitalizations each year, and there is thus a need to personalize drug therapy. With the knowledge and tools available today, we can achieve this at reasonable costs. With over 5,000 articles per year currently being published on genomic markers to guide drug therapy, there is a huge potential. However, some tests are readily accepted by the clinic, but others are not. Surprisingly, these acceptances differ from country to country, and from hospital to hospital. It appears that it is not as much the suggested lack of scientific evidence, but rather other factors that have an impact on clinical implementation, such as education and competition with existing protocols. Our 10 year experience in implementing pharmacogenetics in the Netherlands in clinical diagnostics will be illustrated, covering the value of clinical evidence, education, availability of testing, laboratory and clinical guidelines, quality, feedback from clinicians and patients, reporting, financial and ethical aspects. At Erasmus MC, we currently provide DNA passports for medication, which fits in the trend of a pre-emptive genotyping approach. However, these efforts would not be so successful if not for the early development of a national clinical support system for pharmacists. This system contains evidence-based genotype dependent dosing guidelines for over 80 drugs. So with your DNA passport, you can visit any pharmacy in the Netherlands to obtain medication adjusted on genomic profile. Current challenge is to develop a broader decision support tool, incorporating these dosing advices and coupling directly to an individual’s DNA information in a way that it ensures optimal access to this information for health care provider as well as individuals.

Birgit Strodel

Professor of Computational Biochemistry, Jülich Research Centre, Germany & Department of Chemistry, Heinrich Heine University Düsseldorf, Germany
Strodel Lab

Talk title: Advances and challenges in the simulation of protein aggregation at the atomistic scale

The aim of Birgit's work is to understand the physico-chemical principles that govern the highly complex process of protein aggregation. This process may lead to fatal diseases, as in the case of Alzheimer's disease, but we can also profit from it in the form of novel nanomaterials. All-atom molecular dynamics (MD) simulations of protein aggregation in explicit solvent have been performed for over a decade, revealing valuable information about this phenomenon. However, all studies published to date suffer from at least one if not both of the following two problems: (1) The accuracy of current all-atom force fields in modelling disordered proteins and protein aggregation is insufficient as recent benchmark studies revealed. (2) The second problem is that all-atom MD simulations of protein aggregation are generally performed at protein concentrations orders of magnitude higher than the comparable in vitro and in vivo situations, limiting structural rearrangements between aggregate growth events. In the presentation Birgit will explain how the latter limitation can be overcome by extending the formalism of Markov state models to study protein aggregation.