In this issueFeature
Candid candidiasis research
The word ‘candida’ usually makes us think of inconvenient, yet relatively harmless fungal infections. Some species of candida are normal flora and live on our skin and in the gastrointestinal tract, controlled by the skin and the body’s own chemicals. If the fungus, however, enters the bloodstream through irritated tissues, it can cause infection in the blood, heart, brain, bones, eyes, and other parts of the body. In fact, severe fungal infections claim an estimated 1.5 million lives each year. Immunocompromised people are most at risk.
Professor Wally Langdon at The University of Western Australia is perhaps best known for his leukaemia research. He was recently awarded as the ‘Cancer Researcher of the Year’ by the Cancer Council WA in recognition for 30 years of vital cancer research. Prof. Langdon’s varied research interests have also extended to studying severe fungal infections because of his collaboration with two groups who have made many important discoveries investigating the role of Cbl (Casitas B-lineage lymphoma) proteins in immune regulation.
In his two recent papers, both published in Nature Medicine, Prof. Langdon and his colleagues investigate the gene Cblb in relation to candidiasis. Both studies used a Cblb knock-in mouse model generated by Ozgene that inactivates Cblb’s E3 ubiquitin ligase activity. According to the publications, disseminated candidiasis and fungal sepsis are some of the leading causes of life-threatening fungal infections. Treatment options are limited since the mechanisms that protect us from candidiasis are not known.
One of the papers (Xiao et al. 2016) reported that Cblb deficiency or inactivation protected mice from lethal systemic infection of Candida albicans. However, deficiency of dectin-1, dectin-2, or both in Cblb−/− mice negated the protection. This data provides the first evidence that Cblb plays an essential role in regulating dectin-mediated innate immune responses to fungal infections. This suggests that targeting Cblb could serve as a new therapeutic strategy.
The other paper (Wirnsberger et al. 2016) also found that genetic deletion or inactivation of Cblb protected mice and improved survival after a systemic lethal Candida albicans infection. Based on these findings, a cell-permeable Cblb inhibitory peptide was engineered. Treatment of mice with the inhibitory peptide significantly improved immune function toward Candida albicans and protected mice from a lethal infection. This study presents a novel therapeutic approach to enhance antifungal immunity.
For more information on Prof. Langdon’s research, read the two publications below and visit the The University of Western Australia website.
For more information on Ozgene mouse models, please see Ozgene services.
Happy Holidays from Ozgene
Thank you to all of our clients and collaborators for the past year. We hope you have a relaxing holiday season and look forward to continuing to work with you in 2017. We are in the process of expanding our phenotyping services in the New Year and reducing our timelines even further to get your research moving sooner. As always, feel free to contact us for a confidential discussion on your research needs.
FEATURED - Nat Med. 2016 Aug.
Targeting CBLB as a potential therapeutic approach for disseminated candidiasis.
Xiao Y, Tang J, Guo H, Zhao Y, Tang R, Ouyang S, Zeng Q, Rappleye CA, Rajaram MV, Schlesinger LS, Tao L, Brown GD, Langdon WY, Li BT, Zhang J. - Ohio State University, USA. Central South University; Guangzhou Medical University; University of South China, P.R. China. University of Aberdeen, UK. University of Western Australia, Australia. [read]
FEATURED - Nat Med. 2016 Aug.
Inhibition of CBLB protects from lethal Candida albicans sepsis.
Wirnsberger G, Zwolanek F, Asaoka T, Kozieradzki I, Tortola L, Wimmer RA, Kavirayani A, Fresser F, Baier G, Langdon WY, Ikeda F, Kuchler K, Penninger JM. - Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA); Max F. Perutz Laboratories (MFPL); Vienna Biocenter Core Facilities (VBCF); Medical University Innsbruck, Austria. University of Western Australia, Australia. [read]
Cell Host & Microbe 2016 Nov 9.
IL-17 Receptor Signaling in the Lung Epithelium Is Required for Mucosal Chemokine Gradients and Pulmonary Host Defense against K. pneumoniae.
Chen K, Eddens T, Trevejo-Nunez G, Way EE, Elsegeiny W, Ricks DM, Garg AV, Erb CJ, Bo M, Wang T, Chen W, Lee JS, Gaffen SL, Kolls JK. - University of Pittsburgh School of Medicine, USA. [read]
Frank's blog: Blogs of 2016
December is always a time for reflection. What happened this year? What did we achieve? What can we do better next year? My blogs in 2016 tell a story of learning and discovery...
When all processes produce the desired result first time, the timeline can be as short as 18 weeks.
Our fastest conditional KO project took 20 weeks from vector construction to germline transmission.
The Simple Moving Average timeline of our recently completed conditional KO projects is 33 weeks.