Unraveling the mechanisms of multifunctional antibiotic drugs

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Projektförslag för kandidatarbete inom inst. Kemi och kemiteknik och Biologi och bioteknik
 
​Projektexamenskod: BBTX01-20-03

Avdelningen för Kemisk biologi
Institutionen för Biologi och Bioteknik, Chalmers tekniska högskola 


Bakgrund 
The discovery of antibiotics such as penicillin revolutionized modern medicine. Formerly deadly diseases became easily treatable and infections following childbirth or surgical procedures could be effectively medicated. However, this privileged situation could change drastically over the next years. Bacteria possess a remarkable capability to genetically adapt and become increasingly resistant to existing antibiotics. Only few new antibiotics have been developed in the last decades, which makes it increasingly difficult to keep up with the development of bacterial resistance. To reverse this trend and prevent a fallback into a pre-antibiotic era, we need to advance antibiotic discovery and minimize the development and spread of antibiotic resistance. In order to achieve this, it is essential to understand the molecular mechanisms underlying the activity of antibiotics and the development of resistance.

Problembeskrivning 
​Typically, antibiotic mechanisms are well-characterized in vitro, yet it has been shown that they might have different or additional target structures in vivo. This has major implications on how antibiotic drugs are used, how they might be combined with other drugs, and how resistance against them develops and spreads. Unraveling the in vivo mechanisms of action of antibiotics is one major focus of our research group. Recently, evidence emerged that common antibiotics with established intracellular targets may actually inhibit additional bacterial structures. For example, the ribosome inhibitor tetracycline also targets the bacterial cell membrane and similar evidence has been found for the RNA synthesis inhibitor rifampicin. In this project, the goal is to identify secondary target structures of clinically successful antibiotics. This knowledge is essential to better understand how resistance against these substances develops and to design innovative multifunctional antibiotics of the future.
 
Genomförande /Viktiga moment/teknikinnehåll 
Students will work in small groups to systematically approach their research questions with a range of microbiological methods. The course comprises the following parts:
1. a concise literature review about the known mechanisms of the antibiotics in question
2. design of an action plan based on supplied literature and course materials
3. mode of action analysis of the chosen antibiotics using advanced cell biological methods, different live cell imaging techniques, fluorescence spectroscopy, genetic, and biochemical methods
4. presentation of the research results in the format of a scientific paper


Speciella förkunskapskrav: Students should have a basic understanding of cell and molecular biology and be interested in deepening their knowledge in bacterial cell biology and physiology during the project. The lab language is English and course material will be supplied in English as well.

Möjlig målgrupp This project has a clear focus on bacterial cell biology and is therefore best-suited for students with a background in biology, biotechnology, or biochemistry.

Gruppstorlek: 4–6 studenter 

Förslagsställare/kontaktperson/huvudhandledare: ​Michaela Wenzel, m.wenzel@chalmers.se
Övriga handledare: Ann-Britt Schäfer, annscha@chalmers.se

Publicerad: ti 29 okt 2019.