In order to encourage outstanding doctoral dissertations, the Münchner Bank, the Verein der Freunde und Förderer (VdFF), and the Helmholtz Graduate School Environmental Health (HELENA) again awarded three doctoral prizes this autumn. Each is endowed with 1,500 euros. Matthias Arnold received one of the awards. In an interview, we discussed his doctoral dissertation.
Mr. Arnold, please describe your project.
Unlike monogenic diseases, such as Huntington's disease, in which a single defective gene inevitably leads to an incurable illness, complex diseases such as type 2 diabetes (T2D), asthma, and Alzheimer's are influenced by many different risk factors. Environmental influences and lifestyle play just as much of a role as genetic predisposition. In addition, the two levels interact, and the combination of genetic and external factors together increases the disease risk. Conversely, there are genetic factors that can offset exposure to external risk factors. An example: Obesity is one of the greatest risk factors for T2D, while an active lifestyle is known to reduce the risk. Nevertheless, there are severely overweight non-diabetics, and diabetic half-marathon runners. This personal susceptibility or resilience is at least partially a genetic effect, which infers the sometimes very high heritability rate of complex diseases.
Thanks to modern, high performance screening methods used to determine the variance in the human genome, the number of identified associations between genetic markers and complex diseases is rising rapidly. At the same time, functional studies are uncovering increasingly complex processes involved in the translation from genotype to phenotype, so that functional annotation, meaning the formulation of the suspected effects of genetic variance, necessitates a comprehensive database. My work involves creating such a collection of genomic and phenotypic annotations. This is used to characterize the large part of the genetic variants contained in the human genome at the molecular level. Using this catalogue of variant annotations, which is provided in a freely accessible Genome Browser, demonstrates the advantages of integrative approaches in human genetics at both the global, phenotype-independent level and for selected, case-specific analyses.
How did you hear about the Helmholtz Zentrum München?
The joint degree programme in bioinformatics at the LMU and TUM universities in Munich calls for a number of internships in which one encounters (young) scientists from the greater Munich area, including research groups at the HMGU. A further point of contact was the programme's bioinformatics colloquium. There I asked IBIS employees about a position as a student assistant; I received an offer, and worked there for two years while a student. Following this I was also offered a position there as a doctoral candidate.
How important was the supervision you received during your doctoral work?
The direct supervision has an immense influence on the success and duration of a doctoral project. My supervision structure featured strong contrasts, because my direct adviser left the Helmholtz Zentrum München shortly after I started my doctoral thesis. I consequently began my doctoral work de facto without direct supervision, and the Thesis Committee only theoretically existed. My adviser, Hans-Werner Mewes, encouraged me during this time to contribute to defining the focus of my research myself. And although today my opinion is that these initial difficulties cost me roughly one year, this process allowed my doctoral thesis to have extremely individual focus points, which I have meanwhile come to appreciate greatly. My supervision situation then improved enormously after roughly two years due to a change to the Metabolomics group headed by Gabi Kastenmüller, who then took over my direct supervision. Due to these circumstances, my first Thesis Committee Meeting was unfortunately not possible until after more than two years, but then it was very helpful and motivating.
How important were the offers of the HELENA Graduate School to you?
I very willingly accepted the offer for further training. I would especially like to emphasize, however, that HELENA took my somewhat difficult supervision situation very seriously and provided active support. The embedding of a contact point for doctoral students in the Centre was extremely valuable for me, which is why I was happy to support the Graduate School in carrying out the Environmental Health lecture series as an organizer and in the external evaluation as a speaker. I can therefore also encourage particularly young graduate students to make extensive use of what HELENA offers, especially the Thesis Committee, and, if necessary, the assistance in difficult situations.
What are your plans for the future?
Together with Gabi Kastenmüller, I have raised external funding for my continued employment as a PostDoc. For the medium-term, I plan to gain more experience abroad in the existing cooperation projects with our partners in the USA. We are also working on raising more funds in order to expand our collaboration. Stays abroad and the further development of my scientific profile in the coming years should then form the basis for my next career steps as well as for applications for larger grants.
Mr. Arnold, thank you very much.
Matthias Arnold: Supporting the evidence for human trait-associated genetic variants by computational biology methods and multi-level data integration. More...