Antibiotics-tolerance to multi-drug resistant superbugs: molecular studies

Hovedområde:Molecular Microbiology
 
Målgruppe:Biochemistry, Biology, Molecular Biomedicine
 
Niveau:Masters, Bachelor
 
Projektbeskrivelse:

WE ARE RUNNING OUT OF ANTIBIOTICS…

to eradicate disease-causing bacteria, which have become insensitive to the killing effect of antibiotics. Such antibiotics-tolerant super-bugs will kill more people than cancer by 2050!!! However, we don’t know clearly how these bad bugs (persisters) achieve the ability to tolerate antibiotics.

Over the years, we and others found that the universal signalling nucleotide (p)ppGpp are critical for bacteria becoming antibiotic tolerant. Recently, we made significant progresses in deep understanding of ppGpp:

1) we found new regulators of ppGpp metabolizing proteins that control either the synthesis or degradation of ppGpp, therefore influcencing the ability of bacteria being more tolerant or not.

2) our group, for the first time, successfully identified numerous novel targets of (p)ppGpp in E. coli, some 50 years after the discovery of (p)ppGpp.

3) we found the molecular mechanism of critical Toxin-antitoxin (TA) modules, such as HipBA, in antibiotics tolerance. And more of such TA modules, with some interesting varations, were identified in silico and in various pathogenic bacteria.

We are currently using multi-disciplinary tools such as crystallography, biochemistry and genetics, microscopy, deep sequencing, metabolomics to uncover the molecular details of how the small yet mighty (p)ppGpp turns antibiotics-sensitive bacteria into tolerant states. From there, we could develop novel strategies to re-sensitize the super-bugs to antibiotics.

We therefore are offering exciting BSc, MSc and PhD projects in the above three areas if you care about our future of antibiotics, and have excellent merit, high enthusiasm and ambitiousness.

 
Anvendte metoder:Biochemistry (FPLC,AKTA, enzymology, liquid scintillation, TLC, ITC), Molecular Microbiology (plasmid cloning, genetic screening, genome engineering, phenotyping, plate reader, antibiotics sensitivity assay), system biology (deep sequencing, DRaCALA, metabolomics, proteomics)
 
Keywords:antibiotic tolerance - persistence, ppGpp, multidrug tolerance, superbug, bacterial stress response
 
Projekthjemmeside: https://sites.google.com/view/zhangylab-ucph/home
 
Vejleder(e): YONG ZHANG
 
E-mail:yong.zhang@bio.ku.dk