Pascale Cossart is a French microbiologist specialized in cellular microbiology. Her work focuses on the interactions of bacteria and cells. In particular, she conducted research on the cellular and molecular biology of the bacterium Listeria monoctogenes.
Pascale Cossart is considered a pioneer within the field of "cellular microbiology ", which emerged in the 1990s when molecular and cellular biology approaches converged.
Pathogenic bacteria enter the host organism via the gastrointestinal tract, the respiratory or urinary tract, and, in the case of injuries, through the skin. They can induce a wide variety of diseases and may even lead to death. Pascale Cossart sought answers to questions such as: How does a bacterium select its host, how does it attack it, and how does it ultimately succeed in colonizing it?
She also aimed to identify a variety of bacterial virulence factors and strategies and therefore was able to explain complicated mechanisms that enable bacteria to enter cells and tissues, survive inside them, and spread.
For example, Pascale Cossart showed how a bacterium targets and crosses the body barrier. She also discovered new mechanisms that allow bacteria to downregulate the host's innate immune response. Pascale Cossart also revealed new mechanisms of gene regulation via RNA in particular an RNA thermosensor regulating virulence. Pascale Cossart's research has established the pathogen Listeria as one of the most extensively studied microorganisms and a benchmark reference for infection biology. Her discoveries on this organism revealed mechanisms that other microbes also exhibit and allowed to solve important questions in cell biology.
New techniques and creative approaches, chosen by Pascale Cossart, allowed us to unravel many mysteries concerning the pathways and mechanisms pathogens choose to produce infection.
For further information, please visit: https://research.pasteur.fr/en/member/pascale-cossart/
Jörg Hacker is a bacteriologist who has focused in particular on the molecular biology of bacterial pathogens, including Escherichia coli, Legionella and Staphylococci. Through comparative genome analysis, he has contributed significantly to the understanding of how the transformation from a harmless to a pathogenic bacterial strain occurs.
Hacker was able to describe that uropathogenic Escherichia coli strains spontaneously lose disease genes. It was then shown that these genes are located on large genomic units called pathogenicity islands, which are characterized by a number of specific features. These genetic elements are carriers of numerous properties that give bacteria an advantage in the fight for survival: for example, in the emergence of an infection, in the confrontation with the immune system or in the defense against antibiotics. The virulence factors are preferentially located on gene segments that are mobile and can thus be easily transferred to other bacterial strains. The findings on such gene organization have opened up completely new perspectives on the plasticity of the genetic material of pathogenic microorganisms.
Fur further information, please visit: https://www.leopoldina.org/en/members/list-of-members/list-of-members/member/Member/show/joerg-hacker/
Photo credit: David Ausserhofer für die Leopoldina
David Holden was Director of the MRC Centre for Molecular Bacteriology and Infection at Imperial College London between 2012-2019.
He is a molecular microbiologist best known for inventing signature-tagged mutagenesis (STM, barcoding) for identification of mutants with altered growth in mixed populations. Exploitation of STM and its derivatives has led to phenotypes for thousands of genes of bacterial and fungal pathogens, parasites, yeast and mammalian cells. Holden’s group used STM to discover a multi-functional secretion system required for Salmonella pathogenesis. Subsequently his team characterized the functions of many of its associated effectors that are delivered into host cells and which enable intracellular growth and suppress both innate and adaptive immune responses.
In 2016, Holden was appointed as the first Regius Professor of Infectious Disease in the UK, conferred to Imperial College as part of the Queen's 90th birthday celebrations. He is a Fellow of the Royal Society (UK), the American Academy of Microbiology, the Academy of Medical Sciences and an EMBO Member.
For further information, please visit: https://www.imperial.ac.uk/people/d.holden/research.html
Staffan Normark is a medical microbiologist and senior professor at the Department of Microbiology, Tumor and Cell Biology at Karolinska Institutet. He has been working on the molecular mechanisms that allow pathogenic bacteria to interact with host cells and tissues to cause disease and their tactics to evade host immune responses as well as antibiotic attack. He was born and raised in Umeå in northern Sweden and became professor in medical microbiology at its university 1979. In 1989 he became professor and department head for the Department of Molecular Microbiology at Washington University School of Medicine, St Louis USA where he holds an honorary doctoral degree. He returned to Karolinska Institutet in Stockholm, Sweden 1993. He was a member of the Nobel Assembly at Karolinska Institutet and served in the Nobel Committee for Medicine or Physiology 1996-2001. During 2010-2015 he was a board member of the Nobel Foundation. He became member of the Royal Swedish Academy of Sciences 1987 and was its Permanent Secretary 2010-2015.
Staffan Normark has studied mechanisms by which diverse bacteria are able to colonize host tissues and resist beta-lactam antibiotics. He discovered that beta-lactam antibiotics induce beta-lactamase expression, by increasing production of cell wall fragments (muropeptides) that are taken up into the bacterial cell and sensed by a transcriptional regulator of the beta-lactamase gene. He was the first to dissect in detail the genetic basis of bacterial adhesion. His discoveries led to an understanding of the biogenesis, structure, and role of P-pili of uropathogenic E. coli providing a model and blueprint for receptor-ligand interactions in a number of pathogenic organisms. He discovered that the pilus was a multi-component structure consisting of a stalk and a specialized pilus tip adhesin, and identified key functions of the assembly proteins. Normark also studied the mechanisms for Helicobacter pylori colonization and identified fucosylated blood group antigens as gastric receptors for H. pylori. In addition, he discovered a novel class of adhesive surface organelles on gram?negative bacteria termed curli, which are biofilm promoting bacterial amyloids, determining aspects of their regulation and nucleation dependent assembly. More recently, he has together with Birgitta Henriques-Normark, forged new frontiers in pneumococcal pathogenesis, including identification and role of two classes of pili for adhesion, horizontal gene transfer, and the clonal success of antibiotic resistant strains.
Jörg Vogel has made seminal contributions to our understanding of how cells use noncoding RNA molecules as regulators of gene expression. His research has had its focus on small RNAs in pathogenic bacteria and short and long noncoding RNAs in infected eukaryotic cells. Early contributions include the first systematic screens for small RNAs in E. coli.
Subsequently, he unraveled novel mechanisms elucidating how small RNAs regulate protein synthesis and mRNA decay, and how they recognize mRNAs by conserved short seed pairing domains. More recently, he pioneered the application of emerging deep sequencing technologies to discover regulatory RNAs and their targets on the genome-wide scale in pathogen and host cells.
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