PhD candidate in antibiotic resistance
Faculty of Science – Swammerdam Institute for Life Sciences
The Swammerdam Institute for Life Sciences (SILS) is one of the largest institutes of the Faculty of Science. Its approximately 230 scientists and staff members work in 16 research groups that perform excellent research centered on four themes: 1) Cell & Systems Biology, 2) Neurosciences, 3) Microbiology and 4) Green Life Sciences.
The research group on antibiotic resistance investigates the mechanisms by which microbes become resistant to antibiotics. In this context we are seeking for a PhD candidate to do research on the molecular biology and microbial physiology of the acquisition of resistance.
The aim of the project is to document the chain of events within the microbe that leads to development of de novo resistance upon exposure to antibiotics. The research on molecular mechanisms causing resistance is essential to understand the relationship between exposure and resistance. Several lines of research, including our own, have indicated that the downstream formation of reactive oxygen species (ROS) is a common element in the sequence of events leading to cell death upon exposure to bactericidal antimicrobials. The incorrect mismatch repair after ROS induced DNA damage contributes to the demise of the cell. Possibly the same DNA damage and incorrect repair might in rare cases in individual cells lead to mutations that cause resistance. These cells can grow out and outcompete the other cells in the culture. Large numbers of mutations and DNA rearrangement have been observed during the process of de novo development of resistance.
This project intends to investigate the role of ROS in resistance development from a molecular mechanistic angle. Mutants have already been to identify the formation of 8-Oxo-2'-guanosine and 8-Oxo-2'-dGTP as a crucial step in the ROS-related killing. We intend to use the same or similar mutants to examine the role of these compounds in development of resistance. One part will explore the consequences of the ROS-induced SOS system. Another part will focus on cellular signal transduction, possibly the role of Bi-Cyclic-AMP and other known cellular signals that are part of the system regulating energy metabolism. The role of individual mutations within the cellular signal transduction system will be examined utilizing CRISPR-Cas9 and related molecular techniques.
The knowledge gained in this project can be applied to design optimal treatment protocols and to identify the Achilles heel of the cell in respect to defence against antimicrobial agents. Therefore, it will provide information needed to understand development of resistance, while at the same time identifying targets for more detailed adjustments to application systems that can achieve therapeutic goals at even less resistance costs.
For this position an MSc degree in molecular microbiology or a related field is required. You have proven experimental skills and a good academic record. You are fluent in English, both oral and written. Please specify in your application the laboratory techniques you are familiar with.
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