Overview
Several PhD and post-doctoral positions in computational systems biology are available in the group of Prof. Zavolan at the Biozentrum, University of Basel. Our group is part of the Computational & Systems Biology Program at the Biozentrum and of the Swiss Institute of Bioinformatics. The research in the laboratory revolves around the study of post-transcriptional regulation of gene expression. It is generally accepted that cellular identity of eukaryotic cells is controlled to a large extent by gene expression patterns, and a lot of effort has been invested in studying the mechanisms and principles of control of gene expression by regulation of transcription rates. However, over the last decade it has become increasingly clear that regulation at a post-transcriptional level, i.e. regulation of alternative splicing, of mRNA translation rates, and of mRNA stability, play a crucial role in determining gene expression patterns. Using a combination of experimental and computational approaches our lab aims to unravel the structure and function of post-transcriptional regulatory networks in higher eukaryotic cells. We focus in particular in analyzing the regulation by miRNAs and role of RNA-binding proteins (RBPs).
Job tasks
The positions currently open in our group concern the following three projects:
1. Dynamical aspects of regulation by microRNAs (miRNAs) and the function that miRNAs play in the regulation in gene expression.
Although hundreds of miRNAs have been uncovered in the human genome, and computational and high-throughput experimental studies have determined that a typical miRNA may regulate hundreds of different target mRNAs, the functional role in the gene regulatory network is still unclear for almost all miRNAs. In this project we aim to use computational modeling to elucidate some of the general principles of of miRNA regulation. In particular, in contrast with transcription factors, that target DNA which is essentially always present in a single copy in the cell, the mRNAs targeted by the miRNAs change their concentrations dynamically in response to the post-transcriptional regulation itself. As many miRNAs also target transcription factors which in turn regulate transcription of many of the miRNA targets, it is clear that feed-back loops between transcriptional and post-transriptional regulation are very common. All miRNAs function through binding to a common effector complex, called RISC, so that an effective competition exists between different miRNAs for binding to the effector complex. Moreover, recent work suggests that miRNAs also target the mRNAs of proteins in this effector complex, introducing further feed backs. In this project we aim to develop quantitative dynamical models of miRNA regulation which incorporate the effects of dynamical changes in the concentrations of effector protein and genome-wide targets. Combining computer simulations of these models with targeted follow-up experiments will enable us to estimate model parameters and iteratively perform model improvements with the aim of uncovering the general design and functioning principles of miRNA regulatory networks.
2. The role of RNA-binding proteins (RBPs) in regulating mRNA translation and stability.
Whereas much study has been devoted to DNA-binding transcription factors and their binding specificities, mammalian genomes also encode hundreds of RBPs which regulate the various events in the life of mRNAs, i.e. splicing, transport, translation, decay, and much less is known about the how these RBPs find their targets. Current high-throughput techniques employed in our lab allow us to determine in vivo targets of RBPs on a genome-wide scale. Generally, we aim to develop methods for determining the binding specificities of RBPs, both in terms of primary and secondary structure of RNA, the combinatorial interaction of different RBPs with each other, and the interaction of RBPs with miRNAs in particular. The goal of the project is to develop quantitative models of how RBPs find their targets genome-wide, and how the binding of RBPs to their targets effect translation and mRNA stability.
3. Modeling the role of miRNAs in the regulatory networks that control cellular differentiation in mammals.
Our group is a member of the Cell Plasticity project which is part of the Swiss SystemsX initiative in systems biology. The aim of this project is understand the interplay between transcriptional, post-transcriptional, and epigenetic regulatory networks that are responsible for cellular differentiation processes in mammals (http://www.cellplasticity.org/). Our group will focus on the computational analysis and modeling of the post-transcriptional regulation in these processes. Using computational analysis of large-scale deep-sequencing data from time courses of several different cellular systesm undergoing differentiation we will develop quantitative models for the interplay between the activities of transcription factors that affect transcription rates, and the activities of miRNAs that affect mRNA translation and stability. Predictions from these models will be followed-up experimentally with the long term goal of understanding the role of post-transcriptional regulatory mechanisms in the establishment and maintenance of cell identity.
Profile requirements
We are looking for candidates with a strong quantitative background, i.e. with a M.Sc./PhD (as appropriate) in computer science, computational biology/bioinformatics, physics or mathematics. Candidates should have a experience in programming, preferably in C/C++ and a scripting language like Perl or Python. Importantly, succesful candidates should have a demonstrated ability to perform independent research in computational biology or a closely-related field. Although a formal training in molecular biology is not required, the succesful candidates should have strong desire to develop their knowledge in this area. In addition, there is a tight collaboration between computational and experimental researchers in our group and candidates will be expected to interact closely with experimental colleagues. Postdoc positions are full-time for two or three years. The starting date is flexible and can be determined in mutual agreement.
Please send your application to
Please submit your application letter, a statement of research interests, CV, and the contact information of at least two references to:
Prof. Mihaela Zavolan
Biozentrum Universität Basel
SIB - Swiss Institute of Bioinformatics
Klingelbergstrasse 50-70
4056 Basel Switzerland
email: mihaela.zavolan@unibas.ch This e-mail address is being protected from spambots. You need JavaScript enabled to view it
Please kindly mention Scholarization.blogspot.com when applying for this opportunity
Several PhD and post-doctoral positions in computational systems biology are available in the group of Prof. Zavolan at the Biozentrum, University of Basel. Our group is part of the Computational & Systems Biology Program at the Biozentrum and of the Swiss Institute of Bioinformatics. The research in the laboratory revolves around the study of post-transcriptional regulation of gene expression. It is generally accepted that cellular identity of eukaryotic cells is controlled to a large extent by gene expression patterns, and a lot of effort has been invested in studying the mechanisms and principles of control of gene expression by regulation of transcription rates. However, over the last decade it has become increasingly clear that regulation at a post-transcriptional level, i.e. regulation of alternative splicing, of mRNA translation rates, and of mRNA stability, play a crucial role in determining gene expression patterns. Using a combination of experimental and computational approaches our lab aims to unravel the structure and function of post-transcriptional regulatory networks in higher eukaryotic cells. We focus in particular in analyzing the regulation by miRNAs and role of RNA-binding proteins (RBPs).
Job tasks
The positions currently open in our group concern the following three projects:
1. Dynamical aspects of regulation by microRNAs (miRNAs) and the function that miRNAs play in the regulation in gene expression.
Although hundreds of miRNAs have been uncovered in the human genome, and computational and high-throughput experimental studies have determined that a typical miRNA may regulate hundreds of different target mRNAs, the functional role in the gene regulatory network is still unclear for almost all miRNAs. In this project we aim to use computational modeling to elucidate some of the general principles of of miRNA regulation. In particular, in contrast with transcription factors, that target DNA which is essentially always present in a single copy in the cell, the mRNAs targeted by the miRNAs change their concentrations dynamically in response to the post-transcriptional regulation itself. As many miRNAs also target transcription factors which in turn regulate transcription of many of the miRNA targets, it is clear that feed-back loops between transcriptional and post-transriptional regulation are very common. All miRNAs function through binding to a common effector complex, called RISC, so that an effective competition exists between different miRNAs for binding to the effector complex. Moreover, recent work suggests that miRNAs also target the mRNAs of proteins in this effector complex, introducing further feed backs. In this project we aim to develop quantitative dynamical models of miRNA regulation which incorporate the effects of dynamical changes in the concentrations of effector protein and genome-wide targets. Combining computer simulations of these models with targeted follow-up experiments will enable us to estimate model parameters and iteratively perform model improvements with the aim of uncovering the general design and functioning principles of miRNA regulatory networks.
2. The role of RNA-binding proteins (RBPs) in regulating mRNA translation and stability.
Whereas much study has been devoted to DNA-binding transcription factors and their binding specificities, mammalian genomes also encode hundreds of RBPs which regulate the various events in the life of mRNAs, i.e. splicing, transport, translation, decay, and much less is known about the how these RBPs find their targets. Current high-throughput techniques employed in our lab allow us to determine in vivo targets of RBPs on a genome-wide scale. Generally, we aim to develop methods for determining the binding specificities of RBPs, both in terms of primary and secondary structure of RNA, the combinatorial interaction of different RBPs with each other, and the interaction of RBPs with miRNAs in particular. The goal of the project is to develop quantitative models of how RBPs find their targets genome-wide, and how the binding of RBPs to their targets effect translation and mRNA stability.
3. Modeling the role of miRNAs in the regulatory networks that control cellular differentiation in mammals.
Our group is a member of the Cell Plasticity project which is part of the Swiss SystemsX initiative in systems biology. The aim of this project is understand the interplay between transcriptional, post-transcriptional, and epigenetic regulatory networks that are responsible for cellular differentiation processes in mammals (http://www.cellplasticity.org/). Our group will focus on the computational analysis and modeling of the post-transcriptional regulation in these processes. Using computational analysis of large-scale deep-sequencing data from time courses of several different cellular systesm undergoing differentiation we will develop quantitative models for the interplay between the activities of transcription factors that affect transcription rates, and the activities of miRNAs that affect mRNA translation and stability. Predictions from these models will be followed-up experimentally with the long term goal of understanding the role of post-transcriptional regulatory mechanisms in the establishment and maintenance of cell identity.
Profile requirements
We are looking for candidates with a strong quantitative background, i.e. with a M.Sc./PhD (as appropriate) in computer science, computational biology/bioinformatics, physics or mathematics. Candidates should have a experience in programming, preferably in C/C++ and a scripting language like Perl or Python. Importantly, succesful candidates should have a demonstrated ability to perform independent research in computational biology or a closely-related field. Although a formal training in molecular biology is not required, the succesful candidates should have strong desire to develop their knowledge in this area. In addition, there is a tight collaboration between computational and experimental researchers in our group and candidates will be expected to interact closely with experimental colleagues. Postdoc positions are full-time for two or three years. The starting date is flexible and can be determined in mutual agreement.
Please send your application to
Please submit your application letter, a statement of research interests, CV, and the contact information of at least two references to:
Prof. Mihaela Zavolan
Biozentrum Universität Basel
SIB - Swiss Institute of Bioinformatics
Klingelbergstrasse 50-70
4056 Basel Switzerland
email: mihaela.zavolan@unibas.ch This e-mail address is being protected from spambots. You need JavaScript enabled to view it
Please kindly mention Scholarization.blogspot.com when applying for this opportunity
0 comments:
Post a Comment