Basel Computational Biology Seminar

The lectures take place at Klingelberstr. 61 (vis-à-vis Pharmazentrum), in the lounge on level E13, and start at 16:00h, unless noted otherwise.

Please check below schedule for upcoming lectures. The schedule will be updated regularly.

Prof. Dr. Gilles Charvin
Institut de la Génétique et de la Biologie Moléculaire et Cellulaire IGBMC
Strasbourg, France

Nonlinear feedback drives homeostatic plasticity in H2O2 stress response

Homeostatic systems that rely on genetic regulatory networks are intrinsically limited by the transcriptional response time, which may restrict a cell’s ability to adapt to unanticipated environmental challenges. To bypass this limitation, cells have evolved mechanisms whereby exposure to mild stress increases tolerance to subsequent threats. However, the mechanisms responsible for such adaptive homeostasis remain unknown. Here, we used live-cell imaging and microfluidics to investigate the adaptive response of budding yeast to temporally controlled H2O2 stress patterns. We demonstrate that acquisition of tolerance is a systems-level property resulting from nonlinearity of H2O2 scavenging by peroxiredoxins, and that this regulatory scheme drives a direct hormetic effect of H2O2 on replicative longevity. Our study thus provides a novel quantitative framework bridging the molecular architecture of a cellular homeostatic system to the emergence of non-intuitive adaptive properties.

 

 Date: Monday, February 27, 2016

 Time: 16:00h

 Room: Pharmazentrum, Hörsaal 2

 contact: Vincent Jaquet

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Martin Ackermann
Institute of Biogeochemistry and Pollutant Dynamics
Department of Environmental Systems Science
& Eawag Department of Environmental Microbiology
ETH Zürich

Bacterial memory – scaling up from the behavior of individual cells

Many organisms are able to learn – they store information about the past and use this information to better inform their behavior. Whether bacteria also form ‘memories’ and use these memories for their cellular decision making is less clear. We combine quantitative single-cell experiments with computational modeling to analyze how the behavior of individual cells depends on past events, and how the single-cell behaviors scale up to determine the fate of populations. In our main line of research, we follow single cells of the bacterium Caulobacter crescentus through repeated exposure to stressors and ask whether past exposure allows cells to cope better with future stress. Our first finding is that the link between individual behavior and effects measured at the level of populations is sometimes highly non-trivial; we can only understand population effects by measuring what single-cell do, and using computational modeling to scale to the population level. Our second finding is that bacterial ‘memory’ can be asymmetric, in the sense that only one of the two cells emerging from division reacts to future events in a history-dependent way. Using computer simulations, we find that such an asymmetry in cellular memory could be an evolutionary response to situations where the two cells emerging from division will experience different future conditions. I will also briefly discuss new projects that probe the generality of these findings, and that investigate history-dependent behavior in other bacteria and other biological traits. How organisms operate dynamic environments is a fundamental question, and combining single-cell experiments with modeling can provide new insights into the strategies that microbes use. 

 

Date: Monday, March 20, 2017

Time: 16:00h

Room: Lounge, level E13, Klingelbergstr. 61 (vis-a-vis Pharmazentrum)

contact:  Vincent Jaquet  

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Samie R Jaffrey
Department of Pharmacology
Weill Medical College of Cornell University
New York, NY, USA

The dynamic epitranscriptome: Encoding the fate and function of mRNA with reversible nucleotide modifications

An emerging concept is that an “epitranscriptomic code” of diverse modified nucleotides is found within mRNA and long noncoding RNA, and control their fate and function in cells. This concept was initiated by our transcriptome-wide map of N6-methyladenosine (m6A) which revealed that m6A levels are dynamic, located in at least a fourth of all mRNAs, and enriched in specific regions of the transcript body. Cellular stresses induce an altered pattern of m6A in the transcriptome with notable enrichment in the 5'UTR. These 5’UTR-localized m6A residues confer cap-independent translation to these mRNAs. Next to m6A, the most prevalent modified nucleotide in mRNA is N6,2’-O-dimethyladenosine (m6Am), which is exclusively located at adjacent to the 7-methylguanosine-cap at the first encoded nucleotide in up to 40% of mRNAs. Our transcriptome-wide map of m6Am revealed that m6Am-initiated transcripts are markedly more stable than mRNAs beginning with other nucleotides by rendering the cap resistant to the mRNA-decapping enzyme DCP2. Notably, the fat mass and obesity-associated protein, FTO, demethylates m6Am to 2’-O-dimethyladenosine (Am). FTO shows a marked preference for m6Am compared to m6A, and switches off the stability of m6Am-initiated mRNAs. These findings reveal that epitranscriptomic information is stored in both internal nucleotides and mRNAs caps. 

 

Date: Tuesday, March 28, 2017

Time: 13:00h

Room: Lounge, Klingelbergstrasse 61, level 13 (vis-à-vis Pharmazentrum)

contact: Andrea Riba

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Sophie Brachat, Holger Hoefling 
Novartis Institute for Biomedical Research (NIBR)
Basel, Switzerland

Developing accelerometry based mobility scores, when big data meet big muscle

Physical activity in general, and walking ability (distance, speed, quality) in particular, play a major role as potential patient-oriented clinical outcome measures in many diseases in particular musculoskeletal disorders and are also likely to become highly relevant for health authorities (HA) and payers. Musculoskeletal drugs rely heavily on such robust mobility endpoints for success. Today, HA approved clinical endpoints for physical activity and function are limited to patient reported outcomes (PROs, questionnaires) and variable rapid “snapshot” tests in the clinics (6 minute walk, gait speed). To address this, and in collaboration with our external partners, we have integrated an accelerometry device in 2 of our currently running clinical studies across 132 sites and currently 206 patients are equipped. Sample acceleration in 3 planes is being collected at 100Hz, 24/7 and some patients have now been wearing the device for over a year. We are exploring, developing and benchmarking algorithms to estimate the walking speed of patients in their real-life environment as well as different aspects of the patients gait. In order to explore injury recovery, we have collected longitudinal data on a patient who underwent knee surgery and who has worn the belt for several months and we present results on the improvement of his gait over time after the surgery. 

 

Date: Monday, April 10, 2017

Time: 16:00h

Room: Lounge, level E13, Klingelbergstr. 61 (vis-a-vis Pharmazentrum)

contact:  Gabriel Studer

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Jean-Didier Marechal 
Universitat Autonoma de Barcelona
Barcelona, Spain

CANCELLED

 

Date: Monday, April 24, 2017

Time: 16:00h

Room: Lounge, level E13, Klingelbergstr. 61 (vis-a-vis Pharmazentrum)

contact:  Gabriel Studer

 

 

 

Patrick Müller 
Systems Biology of Development
Friedrich Miescher Laboratory of the Max Planck Society
Tübingen, Germany

Scaling of tissue proportions to body size during vertebrate development

Individuals can vary significantly in size, but the proportions of their body plans are often maintained. To understand how organisms adjust tissue proportions to body size, we analyzed scale-invariant patterning in differently sized zebrafish embryos. By constraining a systematic numerical screen of more than 400’000 models with biophysical in vivo measurements, we computationally identified realistic scale-invariant patterning systems. We tested the predictive power of our “size-dependent inhibition” model with direct experimental manipulations of protein levels and diffusivity in zebrafish embryos, and found that early signaling adjustments in differently sized patterning fields assure the correct proportions of all future tissues.

 

Date: Monday, May 15, 2017

Time: 16:00h

Room: Lounge, level E13, Klingelbergstr. 61 (vis-a-vis Pharmazentrum)

contact:  Richard Neher

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Harmen Bussemaker  
Department of Biological Sciences & Department of Systems Biology & Center for Computational Biology and Bioinformatics at Columbia's Medical Center
Columbia University, New York, NY, USA

Accurate Quantification of DNA Recognition and Methylation Readout by Transcription Factors

Mutations in non-coding DNA are increasingly found to be associated with human disease, yet we currently lack robust methods for predicting transcription factor (TF) binding from sequence, especially at lower affinities. We developed a versatile maximum likelihood framework named No Read Left Behind (NRLB) that fits a biophysical model of protein-DNA recognition to sequencing-based in vitro TF binding data, across the full affinity range. NRLB predicts human Max homodimer binding in near-perfect agreement with existing low-throughput measurements. The model captures the specificity of p53 tetrameric binding sites and discovers multiple binding modes in a single sample. Additionally, we confirm that newly-identified low-affinity enhancer binding sites are functional in vivo, and that their contribution to gene expression matches their predicted affinity. We will also describe EpiSELEX-seq, our method for quantifying the sensitivity of TF binding to cytosine methylation in a context-specific manner, and its application to Hox and bZIP complexes as well as p53. Finally, we will discuss our efforts to decipher the autonomous rules of transcriptional control in human cells using a massively parallel reporter assay named Survey of Regulatory Elements (SuRE), coupled with statistical analysis using generalized linear models.

 

Date: Monday, May 22, 2017

Time: 16:00h

Room: Lounge, level E13, Klingelbergstr. 61 (vis-a-vis Pharmazentrum)

contact:  Andrea Riba 

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Sorry, this talk is cancelled - speaker's flight was cancelled....

 

Gene Yeo
University of California, San Diego, CA, USA

Insights into RNA biology by studying large-scale protein-RNA interactomes and RNA-targeting Cas9

I will present an update on my lab's effort on generating and analyzing protein-RNA interaction maps of hundreds of RNA binding proteins. I will also present our efforts in studying myotonic dystrophy and neurodegeneration using RNA-targeting cas9. 

 

Date: Monday, May 29, 2017

Time: cancelled

Room: Lounge, level E13, Klingelbergstr. 61 (vis-a-vis Pharmazentrum)

contact: Andrea Riba

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This lecture series is part of the graduate teaching program. If you would like to obtain credit points, please sign up for "22830-01 Current research in Bioinformatics I" (fall semester) or "21563-01 Current research in Bioinformatics II" (spring semester). During the first lecture you will be informed on how credit points can be obtained.