A journey through the world of bacteria: meeting friends and foes DATE:
Sunday, May 7, 2017TIME:
2:00 - 3:00 p.m.LOCATION:
Building 2 · Level 5 · Room 5209
In terms of total biomass and diversity, bacteria are arguably the dominant life form on our planet. They interact with humans as commensals (gut microbiota) or pathogens, causing infectious disease. Genetically engineered bacteria are used as cell factories for production of biofuels, various commodities and pharmaceuticals. My first step in the bacterial world was a fundamental study of bacterial signal transduction: protein phosphorylation systems in the model organism Bacillus subtilis. The result of that first step was that one sentence had to be removed from molecular biology textbooks: “Protein tyrosine-phosphorylation does not exist in bacteria”. I will present a brief overview of this journey, from 2003, when my first study demonstrated that bacteria harbor protein tyrosine kinases that phosphorylate endogenous protein substrates, to the current, elaborate map of the tyrosine kinase regulatory network in B. subtilis. In order to study protein phosphorylation in bacteria, we had to develop mass spectrometry proteomics approaches. This effort led to several seminal studies: first introducing site-specific phosphoproteomics, and then quantitative site-specific phosphoproteomics in bacteria.
These advances had the most immediate impact on studies of bacterial pathogens, since protein phosphorylation plays a major role during bacterial infection. My group is currently working on phosphoproteomics to analyze the infection process of Vibrio cholerae and enterotoxigenic Escherichia coli, and several dozen other bacterial pathogens are currently being analyzed using our analytical pipeline world-wide. The next landmark we are aiming at is to get a time-resolved and quantitative phosphoproteome data of an invading bacterium and the eukaryotic host, to capture the phosphoproteome dynamics from both sides of the infection process. This understanding of the infection process is expected to lead to new antibacterial treatments. In the era of antibiotic resistance on the rise, we are focusing on developing antibacterial treatments to which bacteria do not have means of readily developing resistance. We have thus developed a combined treatment of cold plasma and vitamin C which effectively disrupts bacterial biofilms, and a special graphene-based coating for preventing bacterial attachment on medically relevant surfaces. In addition to being very effective, these treatments do not provoke any inheritable adaptation or resistance in bacterial pathogens.
Moving from pathogens to cell factories, my group is generating diverse tools to enhance the metabolism of Bacillus subtilis and Escherichia coli for production of platform chemicals, industrial enzymes and nanoparticles for medical use. We are using protein kinases to engineer phosphorylation controlled transcription factors, we generate promoter libraries, develop CRISPR/Cas9 technology, and use genome-scale metabolic models enhanced with “omics” data to identify optimal targets for metabolic engineering. I will present a case study of introducing and optimizing a heterologous pathway for production of a platform chemical 3-hydropxypropanoate in B. subtilis, which illustrates the metabolic engineering process. I will also present a novel method we have developed: the use of genomics phylostratigraphy as a tool to identify the functions of bacterial “y” genes (with unknown functions). This approach promises to unlock the “hidden” metabolic potential of bacterial cell factories.
The final part of my lecture will focus on demonstrating how our toolbox, comprising metabolic engineering, evolutionary analyses, omics data generation and graphene-based technologies can be implemented to address some of the key challenges at KAUST. Namely, to establish a pipeline for converting the local microbes into potent and robust cell factories. These ideas range from using specially designed graphene flakes for efficient extraction of biofuels from the cell factories, to creating chimeric cell factories uniting the robustness, fast growth and high cell density of Bacilli with the photosynthetic capacity of cyanobacteria.
Ivan Mijakovic is a Chaired Professor of Bacterial Systems Biology and Director of the Area of Advance “Life Science Engineering” at the Chalmers University of Technology (Gothenburg, Sweden), and a Professor of Bacterial Physiology at the Technical University of Denmark (DTU) (Lyngby, Denmark). His research group (http://www.sysbio.se/Lab_Mijakovic/IM_lab.html
) is implanted at the two universities, Chalmers and DTU.
Ivan Mijakovic obtained an Engineering degree in Molecular Biology from the University of Zagreb, Croatia, in 1997. After spending a brief period as Research Associate at the University of Zagreb, he moved to Paris, France, to obtain a PhD degree in Molecular Microbiology from the University Paris XI in 2003. In 2004, he came to the DTU as a postdoctoral fellow, and in 2006 he became Assistant and in 2007 Associate Professor. In 2008, Ivan Mijakovic moved to one of the top Engineering Schools in France: AgroParisTech, as a Professor of Systems and Synthetic Biology. In 2013, he was recruited to the Chalmers University of Technology, as a Full Professor of Bacterial Systems Biology. At the same time, he started a satellite research group at the DTU, first as Professor with special responsibilities (2013-2016), and from January 2017 as Full Professor.
Professor Mijakovic made a number of pioneering contributions in the field of bacterial protein phosphorylation, its physiological role and means of using it to engineer bacterial cell factories or fight bacterial pathogens. His group develops tools for metabolic engineering of bacterial cell factories for production of industrial enzymes, platform chemicals and nanoparticles. The most recent activity in his group is geared toward bio-applications of the advanced carbon material graphene, used for antibacterial coatings and bio-sensors. Professor Mijakovic is an active journal editor (Frontiers in Microbiology, Periodicum Biologorum, guest editor at Journal of Molecular Biology) and conference organizer. He is a recipient of a number of awards for excellence in research and teaching.