News

The Final ImResFun Scientific Conference of the EC-funded Marie-Curie Initial Training Network ImResFun is now announced.

Publication: Candidalysin is a fungal peptide toxin critical for mucosal infection

ITN Practical Course "C2a", Barcelona, Spain (May 10-15, 2015)

ITN Meeting, La Colle sur Loup, France (May 16, 2015)

HPF2015, La Colle sur Loup, France (May 16-22, 2015)

ITN Practical Course "S3" & "C3", Madrid, Spain (July 6-10, 2015)

ITN Mid-Term Review Meeting, Vienna, Austria (November 3, 2015)

ITN Practical Course "S5" & "C5", Tübingen, Germany (May 9-11, 2016)

ITN Lecture Course "S4" & "C4", Szeged, Hungary (July 2-8, 2016)

ITN Practical Course "S6" & "C6", Göttingen, Germany (October 26-28, 2016)

ITN Symposium "S7" & Final Consortium Meeting, Innsbruck, Austria (January 28-30, 2017)

 

Name & Address

Per O. Ljungdahl Portrait

Per O. LjungdahlProfessor of Cell Biology, Chair
Department of Molecular Biosciences, The Wenner-Gren Institute
Stockholm University
Svante Arrhenius väg 20B
Phone: +46-8-164101 FAX: +46-8-159837
e-mail:
Web: http://www.su.se/mbw/

ESR-SU-WG Project: (Start November/December 2013)

Nutrient controlled expression of virulence traits in Candida sop during host colonization

The ESR will complete a rigorous genetic analysis of SPS sensing pathway to monitor fungal virulence and dissemination during host niche colonization by Candida spp. (i.e., organ-specific). This will exploit in vitro / in vivo infection models coupled with bioinformatic analysis to map affected and potentially interrelated genetic regulatory networks. In parallel, the ESR will pursue the development of in vitro biochemical assays of SPS-sensor activation to assess pharmacological modulation by agonists/antagonists.

Main Research Interests

Candida albicans is a commensal organism and one of the many fungi that exist as members of the normal microflora of humans. However, as a consequence of changes in the host environment, and particularly in individuals with a compromised immune system, C. albicans can shift from commensal to pathogenic growth. My laboratory has discovered that C. albicans requires the SPS sensing pathway to respond to amino acids present in the host. This nutrient-induced signaling pathway coordinates the expression of genes required for the efficient uptake of nitrogen for growth, and has the inherent capacity to integrate the catabolic utilization of host proteins and the uptake of amino acids. Importantly, the SPS sensing pathway controls the expression of virulence factors, including secreted aspartyl proteases, and for serum-induced morphological switching that underlies the transition from yeast-like to filamentous growth. We have defined the key signaling events within the SPS sensing pathway, and have a general understanding of how this pathway transmits amino acid-induced signals from the plasma membrane to the promoters of responsive genes. Our studies have illuminated several novel aspects of gene regulation, including receptor-activated proteolysis of latently expressed transcription factors, and transcriptional repression by integral components of the inner nuclear membrane. Also, my laboratory discovered membrane-localized chaperones that function in the endoplasmic reticulum to prevent inappropriate molecular interactions between hydrophobic segments of polytopic membrane proteins as they insert into the membrane. Although these findings appear unrelated, i.e., signal transduction vs. membrane protein biogenesis, our results are highly interrelated. The amino acid sensor in the plasma membrane and the proteins catalyzing amino acid uptake are polytopic membrane proteins that require the same membrane-localized chaperone to be functional expressed. Clearly a broad appreciation of cell biology is required to fully understand cellular signaling systems that underlie C. albicans virulence.

Selected Recent Publications

Davis, M.M., Alvarez, F.J., Ryman, K., Holm, Å.A., Ljungdahl, P.O. and Engström, Y. (2011) Wild-Type Drosophila melanogaster as a Model Host to Analyze Nitrogen Source Dependent Virulence of Candida albicans. PLoS ONE 6: e27434.

Omnus, D.J., Pfirrmann, T., Andréasson, C. and Ljungdahl, P.O. (2011) A Phosphodegron Controls Nutrient-Induced Proteasomal Activation of the Signaling Protease. Ssy5. Mol. Biol. Cell 22: 2754-2765.

Omnus, D.J. and Ljungdahl, P.O. (2013) Rts1-Protein Phosphatase 2A Antagonizes Ptr3-Mediated Activation of the Signaling Protease Ssy5 by Casein Kinase I. Mol. Biol. Cell 24: 1480-1492.