Workshop Molecular Interactions
Berlin, 23rd - 25th July 2008

The research program of the institute encompasses scientific projects on the pathophysiology of inflammation and tumour biology (e.g. NF-kB regulation in inflammation, epithelial differentiation and cell cycle control). Here, the molecular and cell biological mechanisms of the intracellular signal transmission are of special interest. In addition, the research groups work on the question of protein function in cellular networks and the innovative approach of mathematical models of signal processes in complex systems. The offered project comprises work in the understanding of cellular signaling networks (e.g. NF-kB system) relevant for diseases.

The institute allows an internationally competitive research by providing techniques e.g. immunofluorescence, Surface-Plasmon-Resonance (Biacore), proteomics, 2-D / MALDI-TOF / ESI-IONTRAP.

Please send your application to:

Prof. Dr. Michael Naumann

Email: naumann@med.ovgu.de

http://www.med.uni-magdeburg.de/fme/zim/ieim

IMPRS Magdeburg, Winter Term 2008

Prof. Gilles, Systems Biology

http://www.mpi-magdeburg.mpg.de/research/groups/sb

Understanding biological processes from a holistic point of view is only possible with the aid of mathematical modeling attempts. Systems Biology studies the interplay of all interacting components that are relevant for a specific cellular system. It can be expected that this approach will allow better and faster solutions to medical and biotechnological problems.

Available Topics under the supervision of Professor Gilles are:

1.1
Computational modeling the influence of redox signals on the growth mode of purple non- sulfur bacteria (Straube/Gilles)

Purple non-sulfur bacteria follow a versatile life style. When oxygen is available they use the standard respiratory mode of growth via an electron transport chain (ETC) embedded in the plasma membrane. However, if oxygen becomes limited they can also grow photosynthetically using intracytoplasmic membranes that harbor photosynthetic reaction centers and light- harvesting complexes. The formation of these membranes is induced via redox signals from the ETC and can be easily measured in vivo. Recently, we have developed a mathematical model (based on ordinary differential equations) for the ETC which uses the concentrations of cofactors such as ATP/ADP and NADH/NAD as fixed input quantities. It is the aim of the project to extend this model to incorporate the central metabolism such that these cofactors become dynamical quantities whose production and consumption will depend on environmental conditions. In this way we will obtain a more comprehensive understanding of the regulatory mechanisms governing gene expression in response to varying redox conditions of the environment.

Prerequisites:
The successful applicant should have strong interest in modeling large scale metabolic and signal transduction networks. Basic knowledge of nonlinear dynamics and biology are highly appreciated. The applicant is expected to work in an interdisciplinary environment.

IMPRS Magdeburg, Winter Term 2008

Prof. Kaibel, Mathematical Optimization

http://www.math.uni-magdeburg.de/~kaibel/

The scientific work is mainly located in the area of Discrete Mathematics with a strong emphasis on optimization and geometry and the interaction of these two topics. Specific current research topics include:

10.1
Extended Formulations for Discrete Optimization Problems

With this project we focus on a methodical topic that is currently gaining a lot of attention, because it may open new paths to solve discrete optimization problems, which becomes more and more important for research in chemical and biochemical process engineering. The basic idea is to extend the space of variables in which a certain problem is formulated by additional ones and then to determine a suitable linear description of a polyhedron in that extended space whose projection to the original variables gives the convex hull of the solutions to the problem under investigation. Such extended formulations have been discovered for several individual problems (e.g. problems that can be solved by dynamic programming algorithms of a certain type or special mixed-integer optimization problems). A fundamental question that is unsolved asks whether there is a polynomial size extended formulation for every integer linear optimization problem that can be solved in polynomial time. Yannakakis ("Expressing Combinatorial Optimization Problems by Linear Programs", Journal of Computer and System Sciences, 43, (1991), 441--446) showed that this is not true for the matching problem in case one requires the extended formulation to be symmetric in a sense. One part of this project will be to investigate the role that symmetry plays with respect to extended formulations. Another part consists of investigating the practical impact that the use of extended formulations has at concrete examples. A third part may concern extended formulations of polytopes with respect to the diameters of convex polytopes in view of the simplex algorithm.

Prerequisites:
A good knowledge of linear optimization, combinatorial optimization, integer programing, and the theory of convex polytopes

IMPRS Magdeburg, Winter Term 2008

Prof. Marwan, Molecular Network Analysis

http://www.mpi-magdeburg.mpg.de/research/groups/mna

The behavior of a cell in terms of differentiation, growth, and motility is controlled by networks of interacting biomolecules which are robust but nevertheless responsive to all kind of signals coming from outside or originating from the inner life of the cell. The Molecular Network Analysis Group explores new ways to determine the structure of such networks and to understand their function. In order to consider networks of different levels of molecular complexity, we analyze two biological phenomena, one controlled by a small and one by a large molecular network each providing specific challenges to the researcher, and allowing different types of questions to be addressed. Part of the work is done in close collaboration with the groups of Ernst Dieter Gilles and Dieter Oesterhelt (Martinsried).

Available topics under the supervision of Prof. Marwan are:

3.1
Identification of network modules with hybrid Petri nets (Marwan & Heiner)

The function and fate of living cells is controlled by decision-making molecular networks that process a variety of external and internal parameters sensed through specific receptors to cause cellular responses like motility, proliferation or differentiation. Networks of this kind are important in many aspects of health and disease. Analysing the structure and dynamics of molecular networks is a major issue in systems and synthetic (?) biology, where modelling and simulation play a central role. The proposed PhD project focusses on the design and development of a hybrid Petri net tool, which is able to run models composed of interconnected stochastic, discrete and continuous processes. This hybrid tool will be used to develop procedures to identify, characterise, and reverse engineer molecular circuits as self-contained modules of a global molecular networks. The computational approaches are applied to analyse the cell fate decision in Physarum polycephalum.

Petri nets are powerful computer science models combining an intuitive and executable modelling style with powerful analysis techniques ranging from graph theory via model checking to simulation methods. They provide an elegant, unifying framework for the integration of qualitative, stochastic as well as continuous paradigms.

Prerequisites:
Successful candidates have a strong background in computer science or engineering sciences, are excellent programmers and have a pronounced interest in molecular cell biology.

Relevant References:
Heiner, M.; Gilbert, D.; Donaldson, R.:
Petri Nets for Systems and Synthetic Biology;
in M Bernardo, P Degano, and G Zavattaro (Eds.): SFM 2008, Springer LNCS 5016, pp. 215–264,2008.

Marwan, W., A. Sujatha, and C. Starostzik. 2005.
Reconstructing the regulatory network controling commitment and sporulation in Physarum polycephalum based on hierarchical Petri net modeling and simulation.
J. Theor. Biol. 236:349-365.

IMPRS Magdeburg, Winter Term 2008

Professor Reichl, Bioprocess Engineering

http://www.mpi-magdeburg.mpg.de/research/groups/bpt

Mathematical modeling plays a crucial role in analyzing and optimizing bioprocesses. Without such models, it is practically impossible to quantitatively understand metabolic pathways and regulatory networks of cells, to characterize cell growth and product formation in bioreactors, or to allow for a rational design of several downstream processing steps to maximize yields.

The increasing amount of data available from all levels of a bioprocess – in particular from systems biology approaches - serves as a sound basis on which mathematical models can be formulated. This will eventually not only enable scientists to perform theoretical studies and numerical simulations concerning technical aspects in bioprocess engineering but also support the detailed analysis of the enormous complexity of biological systems.

Available Topics under the supervision of Professor Reichl are:

2.1
Macroscopic models of Influenza A virus entry into mammalian cells used for vaccine manufacturing

Virus diffusion, attachment and entry into its host cell are of major importance for a quantitative understanding of viral infection of mammalian cells. To be modeled correctly these steps must be experimentally characterized, and data fitted to phenomenological dynamic models comprising relevant process steps as well as diffusion time constants, adsorption constants, and endocytosis rates. Therefore, the project covers experimental (equilibrium experiments, receptor binding studies, fluorescence microscopy) and modeling aspects (nonlinear dynamics, modeling tools, model validation).

Prerequisites:
Successful candidates should bring a sound knowledge in mathematical modeling of bioprocesses or theoretical biology plus an interest in experimental work involving mammalian cells, influenza A viruses and microscopical methods.

Relevant References:
Sidorenko, Y. and Reichl, U. (2004): Structured model of influenza virus replication in MDCK cells, Biotechnology and Bioengineering, 88 (1), 1-14.

Reichl, U., and Sidorenko, Y. (2006): Virus - host cell interaction, In: Bioinformatics: From Genomes to Therapies, Lengauer, T., Vol. II, Chapter 23, 861-898, Wiley-VCH.

2.2
Dynamics of microbial communities

Pseudomonas aeruginosa, Burkholderia cepacia and Staphylococcus aureus are opportunistic infectants which occur as mixed cultures in the lungs of cystic fibrosis (CF) patients. Knowledge on possible interactions and growth characteristics of the microbial community in the lung obviously cannot be obtained in situ.

Therefore, a laboratory chemostat is used to quantitatively study the three species as a reproducible mixed culture under completely defined and controllable conditions. Experiments show an apparent coexistence of at least two of the species for more than 32 volume exchanges, a result not predictable with a model assuming pure substrate competition.

To better understand the dynamics of this system mathematical models should be further developed and simulation results compared to experimental data comprising absolute cell counts and metabolic data.

Prerequisites:
Successful candidates should bring a sound knowledge in mathematical modeling of bioprocesses or theoretical biology plus an interest in experimental work involving microorganisms and bioreactors.

Relevant References:
Schmidt, J.K., König, B., Reichl, U. (2007): Characterization of a Three Bacteria Mixed Culture in a Chemostat: Evaluation and Application of a Quantitative Terminal-Restriction Fragment Polymorphism(T-RFLP) Analysis for Absolute and Species Specific Cell Enumeration, Biotechnology & Bioengineering. 96 (4), 738-756.

Heßeler, J., Schmidt, J.K., Reichl, U., Flockerzi, D. (2006): Coexistence in the chemostat as a result of metabolic by-products, Journal of Mathematical Biology, 53 (4), 556-584.

IMPRS Magdeburg, Winter Term 2008

Prof. Warnecke, Institute for Analysis and Numerical Mathematics

http://www-ian.math.uni-magdeburg.de/home/warnecke/

The group is focused on research concerning numerical methods for partial differential and integral equations. This includes research on the mathematical properties of algorithms such as their consistency, convergence, stability, and their ability to maintain important qualitative properties of solutions such as conservation principles or positivity. Insight gained from the mathematical analysis of algorithms is used to develop faster and more accurate computational methods. The areas of application include compressible multi-phase or multi-component flow including phase transitions, reaction-diffusion systems, and population balance equations for aggregation, breakage and growth of particles. The principal researchers in this group have many years of experience in the cooperation with engineers and physicists on such topics.

Available Topics under the supervision of Professor Warnecke are:

11.1/11.2
Numerical methods for population balance equations with high property space dimension, 2 subprojects (Warnecke, Sundmacher, Kienle/Reichl)

The topic will consist of at least two subprojects for two doctoral students that should cooperate with each other and with colleagues and students from engineering at the Max-Planck Institute (MPI) and the faculties of processes (FVST) as well as electrical (FEIT) engineering .

We want to develop and improve numerical methods for these integro-differential equations. The first step will be the proper identification and formulation of multidimensional models, i.e. the equations that we want to discretize numerically. Multi-dimensional equations require a great efficiency of the discretization of these as well as in the numerical treatment of the discretized problems. These are interlinked and should not be treated separately.

The first model (9.1) will come from a project on precipitation processes in droplets of emulsions used in the group of Professor Sundmacher. It describes the agglomeration of droplets containing concentrations of various substances. A similar model is available for multicomponent aerosols. The second model (9.2) will come from emerging new field of bio-process engineering with applications to virus replication in conjunction with the research groups of Professors Kienle (MPI/FEIT) and Reichl (MPI/FVST). Here the model has to be fully established in cooperation with the participating engineers. We plan to study to two types of multi-dimensional problems. The first are those with moderate sizes of dimension and those with much higher dimensions. This is an emerging field and we should explore some currently discussed techniques.

11.3
Numerical methods for population balance equations coupled to external fields (Warnecke, Seidel-Morgenstern)

The topic will be pursued in conjunction with specific applications in preferential crystallization of enantiomers. This process has important technological applications, e.g. for medical drug production. The interest is in numerical methods for systems of equations where population balances for growth are coupled e.g. with mass balances. The latter are needed in order to provide overall mass conservation.

IMPRS Magdeburg, Winter Term 2008

Prof. Weismantel, Institute for Mathematical Optimization

http://www.math.uni-magdeburg.de/~weismant/

The current research addresses questions in the area of discrete mathematics and optimization. Research focuses on topics from integer programming, algorithmic discrete mathematics, combinatorial optimization and algorithmic geometry of numbers. The scope of applications ranges from chemical engineering and control theory to cell biology.

Available Topics under the supervision of Professor Weismantel are:

12.1
Combinatorial algorithms for hypergraphs with applications to signal transduction networks

Different aspects of biological systems as, e.g., regulatory or signal transduction networks, can be modeled as combinatorial optimization problems on hypergraphs (that are families of subsets of a ground set). Such problems are NP-hard integer optimization problems and, therefore, knowledge on the structure of the involved hypergraphs or associated polyhedra is required in order to design suitable combinatorial algorithms which solve the given problems exactly and in a reasonable time. The goal of this project is to investigate whether the involved hypergraphs belong to a class for which polynomial solvability is known, to transform the given hypergraphs into a member of such a class (e.g., with the help of the integral basis method), or to design new algorithms which perform well on the studied hypergraphs.

Prerequisites:
Sound knowledge in combinatorial optimization, polyhedral combinatorics, integer programming.

12.2
Mixed-integer polynomial optimization for the optimal synthesis of integrated reaction-separation processes

In chemical industry the synthesis of many products is based on a chemical reaction in combination with a separation step. The goal is to realize such integrated synthesizes in an optimal way. A suitable (mathematical) model must reflect the kinetic of the underlying chemical reaction, satisfy several material balance equations, and include a suitable cost function, which leads to a non-linear mixed integer (polynomial) optimization problem. Due to non-convex terms involving both continuous and discrete variables, problems of this kind are typically extremely difficult to solve to global optimality. The goal of this project is to study real-world processes, developing new mathematical methods as required.

Prerequisites:
Sound knowledge in linear and combinatorial optimization, integer programming, and in multidimensional analysis or differential geometry

The MAX DELBRÜCK CENTER FOR MOLECULAR MEDICINE (MDC) BERLIN-BUCH is inviting applications for the following positions:

Independent Junior Group Leader Positions, Systems Biology

(5 years, Tenure track)

The MDC Berlin-Buch is a member of the Helmholtz Association of National Research Centers, supported by the Federal Government of Germany and the Land Berlin. It is a biomedical research institute dedicated to interdisciplinary research in the areas of Cardiovascular and Metabolic diseases, Cancer and Function and Dysfunction of Nervous System.

The MDC is committed to expanding its impact in the field of Systems Biology, especially through the project ‘Berlin Institute for Medical Systems Biology’ funded by the BMBF and the Senate of Berlin. The MDC is seeking applications from outstanding individuals working in areas of functional genomics, medical systems biology and computational biology. Applicants using high-throughput genomics and proteomics technologies for research on genetic variation, RNA Biology, bioinformatics for analysis, prediction and modelling are encouraged to apply.

Successful candidates will conduct independent research, obtain extramural funding and engage in collaborative projects with groups at the MDC and the MDC Project ‘Institute for Medical Systems Biology’ lead by Prof. Nikolaus Rajewsky.

For further information about the MDC Berlin-Buch please visit our web site (http://www.mdc-berlin.de and the Rajewsky research team-site: Systems Biology of Gene Regulatory Elements). Enquiries about the scientific positions and perspectives should be addressed to Prof. Dr. Nikolaus Rajewsky (rajewsky@mdc-berlin.de).

Applications should be sent by August 23, 2008, including curriculum vitae, list of publications, outline of present and planned research and/or other relevant material in print to:

Prof. Dr. Walter Birchmeier, Scientific Director

Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch

Robert-Rössle-Str. 10, 13125 Berlin-Buch, Germany

Electronic submission of your application (in one pdf-file) should be addressed to: bewerbung@mdc-berlin.de.

The MAX DELBRÜCK CENTER FOR MOLECULAR MEDICINE (MDC) BERLIN-BUCH is inviting applications for the following positions:

Group Leader position for a scientific Core Group Bioinformatics/Quantitative Biology,

Postdoctoral Positions in experimental and computational Biology and Bioinformatics,

System Administrators and

PhD students

The ‘Berlin Institute for Medical Systems Biology’ is funded by the BMBF and the Senate of Berlin and has the mission to complement and build up research, technology and excellence in Systems Biology at the MDC and in collaboration with Berlin Universities and Research Centers in Berlin. The scientific focus of the Institute will be in the field of RNA Biology, genetic variability, models and modelling of complex diseases.

The focus of the Bioinformatics Scientific Platform will be data handling and processing of large scale applications like Deep Sequencing, Chip Technology and Mass Spectrometry as well as computational analysis and modelling of biologic processes.

For further information about the MDC Berlin-Buch and please visit our web site (http://www.mdc-berlin.de and the Rajewsky research team-site: Systems Biology of Gene Regulatory Elements). Enquiries about the scientific positions and perspectives should be addressed to Prof. Dr. Nikolaus Rajewsky (rajewsky@mdc-berlin.de), further enquiries should be addressed to Alexandra Tschernycheff (tschernycheff@mdc-berlin.de).

These positions are funded according to the German TVöD-System.

Applications should be sent by August 23, 2008, including curriculum vitae, list of publications, outline of present and planned research and/or other relevant material in print to:

Personalbteilung, Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch

Robert-Rössle-Str. 10, 13125 Berlin-Buch, Germany

Electronic submission of your application (in one pdf-file) should be addressed to: bewerbung@mdc-berlin.de.