Please also have a look for student projects within the Zamboni group .
Student research (3 month) and Master thesis projects are available in the following areas: Systems biology of bacterial or yeast metabolism, Quantitative metabolomics (mass spectrometry), Analytical chemistry, Biofuels.
Below the titles of available projects. Further down you can find details of each project.
Tutor: Zrinka Raguz Nakic (firstname.lastname@example.org)
Duration: Master project
As the most important post-translational modification, phosphorylation can alter the activity of proteins in various ways. While modern phosphoproteomics generates huge catalogues of protein phosphorylation sites for many organisms from bacteria to human tissues, we know extremely little about the function of these phosphorylation events. Typically, functionality of a specific phosphorylation site has been achieved in less than 1% of the cases.
In the bacterium E. coli, the impact of phosphorylation on the regulation of the active protein pool is so far widely unknown. Phosphorylation has been studied solely at the descriptive level by phosphoproteomics and the functionality of the described phosphorylation sites has never been addressed in a systematic manner.
This project is a collaboration with the Columbia University about the systematic elucidation of the functional relevance of phosphorylation in E. coli. We already have a collection of single point mutations in the phosphosites of all phosphoproteomically observed E. coli phosphorylation sites related to metabolism.
In your project, you will physiologically characterize the mutants using microtiter plate cultivation. You will use untargeted mass spectrometry for metabolites measurements, thereby taking metabolism as a direct readout for the effect of the individual mutations, allowing you to characterize the functional role of the mutated phosphorylation sites.
Ultimately, your project will help to give novel insights into the yet unknown role of phosphorylation in regulating metabolism in E. coli.
The project requires interest in both, wet lab as well as computational data analysis. Matlab experience is not a requirement, but helps.
Interested? Send me an email or drop by for a coffee (HPT D58).
Tutor: Daniel Sévin (email@example.com)
Duration: 3 to 6 months
Start: September/October 2012
Most known enzymes are assumed to be specific, meaning that they accept only a small set of substrates which they convert into products via a specific reaction mechanism. This historical ‘one enzyme – one function’ perspective, however, is challenged by recent experimental evidence suggesting that promiscuity – i.e., the ability of an enzyme to catalyze multiple reactions – could be far more prevalent than it is currently acknowledged. It appears that many enzymes seem specific only because their additional functions have not yet been discovered, mainly due to the fact that usually once an enzyme has been associated with a certain function no further inquiries about alternative activities are made. Understanding the extent of enzyme promiscuity has profound implications on our perception of the function and evolution of metabolism. However, the actual level of promiscuity among known enzymes so far has never been systematically investigated, mainly due to the lack of suitable experimental approaches.
We have developed an experimental in vitro metabolomics method that, for the first time, allows to systematically probe large numbers of enzymes for eventual promiscuity. E. coli possesses 1366 known metabolic enzymes with at least one established catalytic activity, and in your project, you will apply this novel method to systematically screen these enzymes for promiscuous activities.
During the project, you will learn basics of bacterial cell cultivation, high-throughput protein purification, high-resolution non-targeted mass spectrometry and computational data analysis. The results you obtain will help to shed light on the prevalence of catalytic promiscuity in E. coli, a phenomenon that might have considerable implications for our understanding of metabolic function and evolution.
Interested? Just send me an email or drop by in my office (HPT D73) for a coffee!
Allosteric regulation of protein activity by small molecules is a highly conserved form of regulation. In particular, allosteric interactions between enzymes and metabolites play a vital role in the regulation of metabolism. So far, however, the identification of allosteric interactions requires time-consuming in-vitro experiments, and there is a pressing need for approaches which allow the identification of such interactions using in-vivo data. Moreover, there is so far no systematic way to determine the function of specific interactions in the regulation of metabolism.
In your project we ask whether increasing abundance of an allosteric enzyme is compensated by changes of its effector metabolites. To answer this question you combine state-of-the-art metabolomics, high-throughput cultivation and genetics. Initially, you will construct a small plasmid library which allows altering the abundance of key metabolic enzymes, and you will characterize the cellular response to these perturbations by measuring physiology and metabolome. In a next step, you will employ correlation analysis to identify potential interactions between metabolites and enzymes and their function in regulating metabolism.
This project is suitable for a student research project (3 months) or master thesis (6-9 months), and it fits you if you have a general interest in systems biology and metabolism. No prior experience in metabolomics is required.
Interested? Send us an email or drop by for a cup of coffee (D73/D52).
Mycobacterium tuberculosis is the causing agent of tuberculosis (TB), which worldwide is responsible for 2 million deaths annually. TB occurs in two phenotypes. In the ‘active’ form the bacteria are replicating, while in the ‘latent’ form of the diseaseno bacterial growth is observable. This latter form causes tremendous problems in the treatment of patients, as the dormant bacteria reside in pathogenic structures that lead toincreased resistance to a broad spectrum of antibiotics. Consequently, these non-growing subpopulations of persisting tubercle bacilli are the main reason for the prolongation ofcumbersome drug treatments and hence a primary research area for novel therapeutic approaches.
Only recently, it has been shown that dormant mycobacteriadepend on a reduced, but active metabolism for long-term survival. Hereby, limited supply of oxygen and nutrients are believed leading to an altered physiology of the cells. However, systematic experimental investigations aiming at a better understanding of the bacilli’s metabolism during persistency are missing up to date.
You will work with different experimental model systems of mycobacteria’s dormancy state. In a first step you will characterize physiological states by parameters such as survival and substrate uptake rates. Subsequently, you will analyze the persistent mycobacteria’s metabolome in more detailed investigations and track specific metabolites by isotopic labeling experiments.
In this project you will learn various standard procedures for the work with microorganisms in general and with Mycobacterium ssp. in particular. Furthermore, you will apply metabolic measurements, for which you will get familiarized with analytical methods based on mass spectroscopy such as LC-MS/MS and GC-MS.
Interested? Send me an email or drop by for a cup of coffee (HPT D60).
To cope with perturbations in the environment, cells have developed a series of mechanisms to regulate their metabolic activity. In bacterial organisms such as E. coli, transcriptional regulation is the main regulatory mechanism. Much of the functional interplay across the metabolic and transcriptional network is implemented by key allosteric interactions between transcription factors and metabolites. Understanding the quantitative, dynamic and single cell nature of such regulatory feedbacks is key to unravel the principles of metabolic regulation.
This project is primarily experimental but requires the use of simple models to study transcriptional regulation. Thus, the project is an ideal hand-on introduction to quantitative modelling for biologists that have had limited or no computational experience. The goal is to investigate the extent of metabolic feedbacks that regulate genes in central metabolism by analyzing their gene expression across different environment conditions in both population and single cell resolutions. You will learn how to use fluorescent promoter reporters and high-throughput cultivation devices, microscope and FACS technology to measure gene expression at population and single cell resolution. You will use a simple quantitative description of gene expression in the form of thermodynamic modelling to infer from data the key parameters that control gene expression. As initial focus, you will concentrate on promoters controlled by two key global regulators of E. coli metabolism that have been previously linked to metabolic feedback mechanisms. This semester project fits you if you fancy quantitative biology and would like to explore the difference between understanding biological functions at the population and single cell level.
Interested? Send us an email (see above) or just drop by for a chat (HPT D73/D58).
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