Bachelor- Master Project or Thesis

Bachelor- Master Projects or Thesis in our research group

 

In different research projects we offer various student projects in the following areas:

 

"Identification and optimization of small molecules for reprogramming"

Embryonic stem (ES) cells are considered to offer high potential for therapeutic application and in particular as a source for regenerative medicine. Reprogramming of mature somatic cells from adults into an ES-like cell, termed “induced pluripotent stem cell” (iPS), may provide a potential approach to obtain cells in a pluripotent state, from which cells for specific therapeutic applications can be derived. These type of cells will have the genetic properties of the patient (donor), thus immunreactions connecte with foreign cells can be circumvented and  ex-vivo patient phenotype-based drug screens could be performed. One well-established and most widely spread method for generation of iPS is the transfection with viral vectors for the expression of stem cell specific transcription factors, like Oct3/4, Sox2, Lin28, Nanog, Myc and Klf4. A disadvantage of this approach is that it leads to changes in the genome and may lead to further mutations, which could translate into adverse effects in the host. There is evidence that small molecules can facilitate this process and may help to overcome limitations of genetic reprogramming protocols. We screen for substances that can be used in the context.

Chemistry: Chemical synthesis of derivatives of a lead structure and screening for biological activity in cell based luciferase reporter assays.

Biology: In detailed analysis of a selected compound by various cell based and biochemical assays, including online-luciferase monitoring, immunoblot, qRT-PCR and FACS.

Contact details:
Dr.  Xinlai Cheng and
Prof. Dr. Stefan Wölfl
Institute for Pharmacy and Molecular Biotechnology
University of Heidelberg
Im Neuenheimer Feld 364, OG. 5, Room 512

Tel: 06221/544859
email: x.cheng@uni-heidelberg.de


"Small molecule that targets cancer and cancer stem cells"

A large number of experimental results suggest the existence of a subpopulation of self-renewable cells within tumors, termed cancer stem cells (CSCs), that initiate tumor development, sustain growth and lead to resistance to conventional chemo- and radiation therapy. Therefore, small molecules that specifically target CSCs could provide a big advantage in cancer therapy. Pancreatic ductal adenocarcinoma (PDAC), the most common type of pancreatic cancer is one of the most uncurable tumors with less than 5% of 5-year survival rate. It has been reported that some pancreatic cancer cell lines contain high levels of CSC.

Using this model system we aim to identify small molecules that specifically target the CSC population within these cell lines. We further want to analyze how metabolism and respiration can modulate the sensitivity of tumor cells to drug treatment.  

 

Analyze cellular subpopulations by flow cytometry (FACS) and investigate the
influence of growth conditions on cancer (stem cell) survival.

Analyze the transition (trans-differentiation) between cell types using markers for epithelial-mesenchymal transition (EMT).

Identify the protein(s) responsible for drug resistance under specific growth conditions and generate resistant/sensitive
cell lines using knock-down and overexpression constructs.  

We offer excellent research conditions in modern laboratories and in an interdisciplinary research environment.

 

Contact details:
Dr.  Xinlai Cheng and
Prof. Dr. Stefan Wölfl
Institute for Pharmacy and Molecular Biotechnology
University of Heidelberg
Im Neuenheimer Feld 364, OG. 5, Room 512

Tel: 06221/544859
email: x.cheng@uni-heidelberg.de


"Isolation of intact mitochondria for the analysis of mitochondrial activity in response to drug treatment".


In this project an interested student will be involved in the investigation of drug induced apoptosis mechanisms. The training and work will include, basic methods of molecular cell biology, cell fractionation, isolation of cellular compartments with an emphasis on isolation of intact mitochondria and the optimization of functional assays with the isolated mitochondria. The assays will be used to study the influence of apoptosisinducing candidate drugs on mitochondrial activity.

Our lab has a focus on bioanalytics and drug research. We provide the opportunity to work with a wide range of powerful experimental tools and (unique) laboratory equipment in a motivating and stimulation research environment. We have the required know how and will provide extensive support in particular on the biochemical background of the work. The projects are especially suited for students that want to develop methods that are used in a biotechnological and bioanalytical setting.

 

Contact details:
 Prof. Dr. Stefan Wölfl
Institute for Pharmacy and Molecular Biotechnology
University of Heidelberg

 


Development of computer controlled experimental processes
for microbiology and biochemistry

 

Our group offers two interesting internship projects (min. 6 weeks) that could be extended into a bachelor- master- or diploma thesis.

1. Development of an object oriented infrastructure for handling compounds in a liquid handling system

We have implemented a system for carrying out automated and computer controlled microbiological experiments using a pipetting robot and an attached plate reader. R scripts are used to control the hardware and vary the experimental parameters. We currently use the system for investigating the dependence of enzymatic activity on modulators and environmental conditions and the growth of microorganisms in differently composed media. The goal of the first project is to develop an object oriented design for representing substances, their concentrations and identities and the vials they are in. The new classes should be used to integrated into our framework so that experiments can be described in terms of substance identities and concentrations rather than vial positions and volumes. This additional layer of abstraction should be used to automatically choose between different dilutions and vials and minimize pipetting inaccuracies by choosing the optimal set of stock dilutions for a certain mixture.

2. Implementation of optimal experimental design strategies on an automated experimentation framework

In collaboration with our partners in Norway, we develop biochemical models of condition dependence of enzy-matic activity. We want to determine the parameters of these models by testing different conditions using our robotic system. For this purpose, we want to apply optimal experimental design strategies for choosing optimal mixtures. After performing an initial round of measurements, the model should be refined iteratively by adding new measurements that give a maximum increase in the accuracy of the fitted parameters.

Our lab has a focus on bioanalytics and drug research. We provide the opportunity to work with a wide range of powerful experimental tools and (unique) laboratory equipment in a motivating and stimulating research envi-ronment. We have the required know how and will provide extensive support in particular on the biochemical background of the work.

For both projects, an interested student should have some experience in object-oriented programming, be able to work independently and have interest in developing new research tools that are applied in practice. In addition, the second project requires skills in statistics and general mathematics.

Contact details:
Prof. Dr. Stefan Wölfl
Institute for Pharmacy and Molecular Biotechnology
University of Heidelberg
 

 

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Letzte Änderung: 23.11.2012