DOCSLIB.ORG

5412T1178.Pdf

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
5412T1178.Pdf Cover artwork: Water Memory is by Brisbane artist Judy Watson and features in the new QIMR building Copies of this Annual Report are available on QIMR’s website at www.qimr.edu.au/annualreport and at no cost by contacting QIMR on (07) 3362 0222, freecall 1800 993 000 or by emailing [email protected]. Queensland Institute of Medical Research 300 Herston Road, Herston, Queensland Australia 4006 T: +61 7 3362 0222 F: +61 7 3362 0102 W: www.qimr.edu.au QIMR is committed to providing accessible services to people from culturally and linguistically diverse backgrounds. If you have difficulty in understanding the annual report, you can contact us on (07) 3362 0222 and we will arrange an interpreter to communicate the report to you. ISSN 1839 – 1877 © Queensland Institute of Medical Research 2012 CONTENTS Letter of compliance ...................... 2 Our management ........................ 23 Research highlights ....................... 4 Our performance ......................... 29 Awards and achievements ............. 6 Our research achievements ......... 45 QIMR at a glance ........................... 8 Supporting our research .............. 69 Chairman’s report ........................ 10 Financial statements .................... 73 Director’s report ........................... 11 Supporting information .............. 115 Our organisation .......................... 13 Compliance checklist ................. 146 Our people .................................. 16 Acronyms .................................. 148 Our governance ........................... 17 LETTER OF COMPLIANCE 31 August 2012 The Honourable Lawrence Springborg MP Minister for Health Parliament House BRISBANE QLD 4000 Dear Minister I am pleased to present the Annual Report 2011–2012 and financial statements for the Council of the Queensland Institute of Medical Research. I certify that this Annual Report complies with: • the prescribed requirements of the Financial Accountability Act 2009 and the Financial and Performance Management Standard 2009; and • the detailed requirements set out in the Annual report requirements for Queensland Government agencies. A checklist outlining annual reporting requirements can be found on the final pages of this annual report or accessed at our website: http://www.qimr.edu.au/page/About_us/Annual_Report/. Yours sincerely CHRISTOPHER COYNE Acting Chair QIMR Council 300 Herston Road, Herston Q 4006 Australia | QIMR Locked Bag 2000, Royal Brisbane Hospital Q 4029 T (617) 3362 0222 F (617) 3362 0111 W www.qimr.edu.au Page 2 QIMR Annual Report 2011–2012 QIMR is dedicated to translating discoveries into treatments, diagnostics and prevention strategies. Page 3 RESEARCH HIGHLIGHTS Cancer Recruited more than 43,000 Queenslanders for the Completed the third year of a correlative laboratory QSkin study. study in a multi‑centre Phase II lymphoma trial. Developed clinic‑based risk prediction tools Developed an analytical method for the novel for Barrett’s oesophagus, a precursor to anti‑cancer drug EBC‑46, pending Phase I clinical oesophageal cancer. trial in humans. Completed Phase I clinical trial on adoptive Began the national Ovarian Cancer Prognosis and immunotherapy for stage IV nasopharyngeal Lifestyle study (OPAL) looking at how lifestyle factors carcinoma (in collaboration with University of may influence patient outcomes. Hong Kong). Found that overweight and obese women are at Developed a new T cell based therapy for the increased risk of some subtypes of ovarian cancer. treatment of glioblastoma. Generated the first stem cells from patients with Published the first analysis of 20‑year survival rates ataxia‑telangiectasia. for people diagnosed with thin melanomas measuring Discovered novel tissue based biomarkers less than 1mm in thickness. for lymphoma. Discovered that a mutation in the BRCA1 or BRCA2 Developed new diagnostic tools for the rapid genes can improve five‑year survival in ovarian and screening of genes involved in iron metabolism. breast cancer. Identified several new genes and gene mutations that increase the risks of melanoma, and cancers of the breast, ovary, prostate, and endometrium. Page 4QIMR Annual Report 2011–20122010–2011 Infectious Diseases Expanded clinical trials of new malaria drugs and Established a new collaboration with CSIRO to screen vaccines on humans. the CSIRO compound library of more than 20,000 substances, for antimalarial activity. Completed the first‑ever screening for anti‑transmission blocking agents for malaria. Completed a five‑year longitudinal study of schistosomiasis transmission in China. Collaborated on the successful north Queensland release of Wolbachia bacteria to reduce Conducted vaccine trials against a protein from the dengue transmission. schistosome parasite, showing moderate protection. Found that a soil‑based fungus kills dengue mosquitoes in semi‑field testing conditions. Mental Health / Complex Disorders Reported four novel risk genes for migraine Contributed to the world’s largest study of the human without aura. brain, which discovered genes that affect brain size may play a role in intelligence and memory function. Created a stress test that could have application in predicting the risk of developing dementia. Established a clinical trial to test the rheumatoid arthritis drug, tocilizumab, as a new treatment for Created a new model of human eye movement, asthma. to be translated as a tool for the diagnosis of psychotic disorders. Led significant advances in understanding genes and pathways contributing to risk of endometriosis. Discovered a brain imaging marker of genetic risk for bipolar disorder. Discovered that women with a history of endometriosis can have up to three times higher rates of ovarian cancer. Page 5 AWARDS AND ACHIEVEMENTS QIMR’s new research facility was completed in time and under budget, with laboratories commencing their move into the new building in June 2012. The inaugural Rio Tinto Ride to Conquer Cancer benefiting QIMR was held with over 2,000 registered riders participating and raising $4.7 million for cancer research at the Institute. Professor Michael Breakspear (Mental Health and Complex Disorders Program Coordinator) won a 2011 Australian Society for Medical Research (ASMR) Queensland Clinical Researcher Award. Professor Nick Hayward (Oncogenomics) was awarded a William Rudder Travelling Fellowship by the Cancer Council Queensland to promote cancer research in Queensland. Professor Barbara Leggett (Conjoint Gastroenterology) received a Distinguished Research Award from the Gastroenterological Society of Australia. Only one of these is awarded each year. Associate Professor Penny Webb was awarded a National Health and Medical Research Council (NHMRC) project grant of $1.7 million to conduct the world’s first comprehensive study of lifestyle factors that might improve survival for women with ovarian cancer. Dr Manuel Ferreira (Asthma Genetics) received the Ruth Stephens Gani Medal in Human Genetics from the Australian Academy of Sciences for his work on the genetics of asthma. Dr John Miles (Human Immunity) was awarded an NHMRC Career Development Fellowship. Thomas Partridge was awarded a Nuffield Department of Medicine Prize Studentship by University of Oxford. Dr Daniel Buchanan was a finalist in the Gastroenterological Society of Queensland’s 2012 Young Investigator Awards. Page 6QIMR Annual Report 2011–20122010–2011 QIMR’s new research facility was completed in time, with laboratories commencing their move into the new building in June 2012 Page 7 AT A GLANCE BusinessBusiness development development agreements agreements ResearchBusiness development agreements agreements Research service Intellectual property agreements agreements Clinical trial Research serviceLicense Intellectual property agreementsagreements agreements agreements Commercialisation Others agreementsClinical trial License Research service Intellectual propertyagreements agreements agreements agreements Commercialisation Others Clinical trial License agreements agreements agreements Commercialisation Others agreements Patent portfolio 2011-2012 Patent portfolio 2011-2012 Patent portfolio New treatment patents New treatment patents Vaccine patents Vaccine patents Diagnostic patents Drug target Diagnosticpatents patents Drug target patents Page 8QIMR Annual Report 2011–20122010–2011 20000 NHMRC grants 15000 awarded ($ millions) 10000 $MILLIONS 5000 0 2008 2009 2010 2011 2012 YEAR Grants Fellowships 600 Scientific 500 publications 400 300 PUBLICATIONS 200 100 0 2008 2009 2010 2011 2012 YEAR Articles High Impact (publications in journals with impact factors of 10 or more) 600 Staff numbers 500 400 300 STAFF 200 100 0 2008 2009 2010 2011 2012 YEAR Staff Students Page 9 CHAIRMAN’s REPORT The last year has heralded a time of great change and growth Only a year on, these funds are making a big difference to for QIMR. Brisbane residents will notice a change to the lay our researchers. There are currently 27 projects underway, of the land at the Herston precinct, with QIMR’s new 15 floor, thanks to the Ride. These projects are looking at ways to state‑of‑the‑art facility now complete, with laboratories and better treat, diagnose and prevent up to 13 different types of staff beginning the move to their new premises in June 2012. cancers including, skin, melanoma, breast, ovarian, prostate, The new building forms a link between the Bancroft Centre colorectal, brain, blood and lymphoma. Medical research is and the Clive Berghofer Cancer Research Centre and will offer a lot of small
Load more

Recommended publications
  • Investigation of the Underlying Hub Genes and Molexular Pathogensis in Gastric Cancer by Integrated Bioinformatic Analyses
    bioRxiv preprint doi: https://doi.org/10.1101/2020.12.20.423656; this version posted December 22, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Investigation of the underlying hub genes and molexular pathogensis in gastric cancer by integrated bioinformatic analyses Basavaraj Vastrad1, Chanabasayya Vastrad*2 1. Department of Biochemistry, Basaveshwar College of Pharmacy, Gadag, Karnataka 582103, India. 2. Biostatistics and Bioinformatics, Chanabasava Nilaya, Bharthinagar, Dharwad 580001, Karanataka, India. * Chanabasayya Vastrad [email protected] Ph: +919480073398 Chanabasava Nilaya, Bharthinagar, Dharwad 580001 , Karanataka, India bioRxiv preprint doi: https://doi.org/10.1101/2020.12.20.423656; this version posted December 22, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Abstract The high mortality rate of gastric cancer (GC) is in part due to the absence of initial disclosure of its biomarkers. The recognition of important genes associated in GC is therefore recommended to advance clinical prognosis, diagnosis and and treatment outcomes. The current investigation used the microarray dataset GSE113255 RNA seq data from the Gene Expression Omnibus database to diagnose differentially expressed genes (DEGs). Pathway and gene ontology enrichment analyses were performed, and a proteinprotein interaction network, modules, target genes - miRNA regulatory network and target genes - TF regulatory network were constructed and analyzed. Finally, validation of hub genes was performed. The 1008 DEGs identified consisted of 505 up regulated genes and 503 down regulated genes.
    [Show full text]
  • Regulation and Physiological Roles of the Calpain System in Muscular Disorders
    Cardiovascular Research (2012) 96,11–22 SPOTLIGHT REVIEW doi:10.1093/cvr/cvs157 Regulation and physiological roles of the calpain system in muscular disorders Hiroyuki Sorimachi* and Yasuko Ono* Calpain Project, Department of Advanced Science for Biomolecules, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan Received 1 February 2012; revised 16 April 2012; accepted 24 April 2012; online publish-ahead-of-print 27 April 2012 + Abstract Calpains, a family of Ca2 -dependent cytosolic cysteine proteases, can modulate their substrates’ structure and func- tion through limited proteolytic activity. In the human genome, there are 15 calpain genes. The most-studied calpains, referred to as conventional calpains, are ubiquitous. While genetic studies in mice have improved our understanding about the conventional calpains’ physiological functions, especially those essential for mammalian life as in embryo- genesis, many reports have pointed to overactivated conventional calpains as an exacerbating factor in pathophysio- logical conditions such as cardiovascular diseases and muscular dystrophies. For treatment of these diseases, calpain inhibitors have always been considered as drug targets. Recent studies have introduced another aspect of calpains that calpain activity is required to protect the heart and skeletal muscle against stress. This review summarizes the functions and regulation of calpains, focusing on the relevance of calpains to cardiovascular disease. -----------------------------------------------------------------------------------------------------------------------------------------------------------
    [Show full text]
  • Calpain 9 (CAPN9) Mouse Monoclonal Antibody [Clone ID: OTI1C2] Product Data
    OriGene Technologies, Inc. 9620 Medical Center Drive, Ste 200 Rockville, MD 20850, US Phone: +1-888-267-4436 [email protected] EU: [email protected] CN: [email protected] Product datasheet for TA503569 Calpain 9 (CAPN9) Mouse Monoclonal Antibody [Clone ID: OTI1C2] Product data: Product Type: Primary Antibodies Clone Name: OTI1C2 Applications: IF, WB Recommended Dilution: WB 1:2000, IF 1:100 Reactivity: Human, Mouse, Rat Host: Mouse Isotype: IgG2a Clonality: Monoclonal Immunogen: Full length human recombinant protein of human CAPN9(NP_006606) prodced in HEK293T cell. Formulation: PBS (PH 7.3) containing 1% BSA, 50% glycerol and 0.02% sodium azide. Concentration: 0.9 mg/ml Purification: Purified from mouse ascites fluids or tissue culture supernatant by affinity chromatography (protein A/G) Conjugation: Unconjugated Storage: Store at -20°C as received. Stability: Stable for 12 months from date of receipt. Predicted Protein Size: 78.9 kDa Gene Name: calpain 9 Database Link: NP_006606 Entrez Gene 116694 RatEntrez Gene 10753 Human O14815 This product is to be used for laboratory only. Not for diagnostic or therapeutic use. View online » ©2021 OriGene Technologies, Inc., 9620 Medical Center Drive, Ste 200, Rockville, MD 20850, US 1 / 2 Calpain 9 (CAPN9) Mouse Monoclonal Antibody [Clone ID: OTI1C2] – TA503569 Background: Calpains are ubiquitous, well-conserved family of calcium-dependent, cysteine proteases. The calpain proteins are heterodimers consisting of an invariant small subunit and variable large subunits. The large subunit possesses a cysteine protease domain, and both subunits possess calcium-binding domains. Calpains have been implicated in neurodegenerative processes, as their activation can be triggered by calcium influx and oxidative stress.
    [Show full text]
  • Calpain-2 Participates in the Process of Calpain-1 Inactivation
    Bioscience Reports (2020) 40 BSR20200552 https://doi.org/10.1042/BSR20200552 Research Article Calpain-2 participates in the process of calpain-1 inactivation Fumiko Shinkai-Ouchi1, Mayumi Shindo2, Naoko Doi1, Shoji Hata1 and Yasuko Ono1 1Calpain Project, Department of Basic Medical Sciences, Tokyo Metropolitan Institute of Medical Science (TMiMS), 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156- 8506, Japan; 2Center for Basic Technology Research, Tokyo Metropolitan Institute of Medical Science (TMiMS), 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156- 8506, Japan Downloaded from http://portlandpress.com/bioscirep/article-pdf/40/11/BSR20200552/896871/bsr-2020-0552.pdf by guest on 28 September 2021 Correspondence: Yasuko Ono ([email protected]) Calpain-1 and calpain-2 are highly structurally similar isoforms of calpain. The calpains, a family of intracellular cysteine proteases, cleave their substrates at specific sites, thus modifying their properties such as function or activity. These isoforms have long been considered to function in a redundant or complementary manner, as they are both ubiq- uitously expressed and activated in a Ca2+- dependent manner. However, studies using isoform-specific knockout and knockdown strategies revealed that each calpain species carries out specific functions in vivo. To understand the mechanisms that differentiate calpain-1 and calpain-2, we focused on the efficiency and longevity of each calpain species after activation. Using an in vitro proteolysis assay of troponin T in combination with mass spectrometry, we revealed distinctive aspects of each isoform. Proteolysis mediated by calpain-1 was more sustained, lasting as long as several hours, whereas proteolysis me- diated by calpain-2 was quickly blunted.
    [Show full text]
  • Elevated Levels of Calpain 14 in Nasal Tissue in Chronic Rhinosinusitis
    ORIGINAL RESEARCH LETTER Elevated levels of calpain 14 in nasal tissue in chronic rhinosinusitis To the Editor: Recently, calpain (CAPN) 14 was identified by a genome-wide genetic association study to play a role in eosinophilic oesophagitis [1]. CAPN14 expression is also linked with asthma and allergy sensitivity [2]. The overexpression of CAPN14 impairs epithelial barrier function and CAPN14 expression is triggered by Th2-associated signalling, such as interleukin (IL)-13 and IL-4 [3]. CAPNs are intracellular regulatory proteases, and there are 16 members of the human CAPN family. CAPNs perform a number of functions, including cytoskeletal and membrane proteins restructuring, signal transduction and inactivating enzymes involved in cell cycle progression, gene expression and apoptosis [4]. Therefore, our group performed a small pilot study to investigate CAPN gene expression profiles in tissue from another disease associated with eosinophilia and epithelial barrier function, chronic rhinosinusitis (CRS) [5]. Sinusitis is a condition associated with inflammation in the paranasal sinuses and contiguous nasal mucosa and ∼30 million adults report sinusitis symptoms annually in the United States [6]. Sinusitis is deemed chronic if symptoms persist more than 3 months, with most episodes of sinusitis associated with viral upper respiratory tract infections, asthma, allergic rhinitis and exposure to environmental factors, such as cigarette smoke [7]. Steroids are effective in treating sinusitis, thereby underlining the importance of inflammation in disease pathophysiology, with inflammatory cells such as eosinophils linked to nasal polyps formation that contribute to nasal obstruction [8]. Here, we investigated nasal tissue samples collected from patients with documented CRS, who met diagnostic criteria set forth by the Adult Sinusitis Clinical Practice Guideline [9].
    [Show full text]
  • The Pennsylvania State University the Graduate School Department of Biology CONTRIBUTION of TRANSPOSABLE ELEMENTS to GENOMIC
    The Pennsylvania State University The Graduate School Department of Biology CONTRIBUTION OF TRANSPOSABLE ELEMENTS TO GENOMIC NOVELTY: A COMPUTATIONAL APPROACH A Thesis in Biology by Valer Gotea © 2007 Valer Gotea Submitted in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy August 2007 The thesis of Valer Gotea was reviewed and approved* by the following: Wojciech Makałowski Associate Professor of Biology Thesis Advisor Chair of Committee Stephen W. Schaeffer Associate Professor of Biology Kateryna D. Makova Assistant Professor of Biology Piotr Berman Associate Professor of Computer Science and Engineering Douglas R. Cavener Professor of Biology Head of the Department of Biology *Signatures are on file in the Graduate School iii ABSTRACT Transposable elements (TEs) are DNA entities that have the ability to move and multiply within genomes, and thus have the ability to influence their function and evolution. Their impact on the genomes of different species varies greatly, yet they made an important contribution to eukaryotic genomes, including to those of vertebrate and mammalian species. Almost half of the human genome itself originated from various TEs, few of them still being active. Often times, TEs can disrupt the function of certain genes and generate disease phenotypes, but over long evolutionary times they can also offer evolutionary advantages to their host genome. For example, they can serve as recombination hotspots, they can influence gene regulation, or they can even contribute to the sequence of protein coding genes. Here I made use of multiple computational tools to investigate in more detail a few of these aspects. Starting with a set of well characterized proteins to complement inferences made at the level of transcripts, I investigated the contribution of TEs to protein coding sequences.
    [Show full text]
  • Calpain-5 Expression in the Retina Localizes to Photoreceptor Synapses Kellie A
    University of Kentucky UKnowledge Spinal Cord and Brain Injury Research Center Spinal Cord and Brain Injury Research Faculty Publications 5-2016 Calpain-5 Expression in the Retina Localizes to Photoreceptor Synapses Kellie A. Schaefer University of Iowa Marcus A. Toral University of Iowa Gabriel Velez University of Iowa Allison J. Cox University of Iowa Sheila A. Baker University of Iowa See next page for additional authors Right click to open a feedback form in a new tab to let us know how this document benefits oy u. Follow this and additional works at: https://uknowledge.uky.edu/scobirc_facpub Part of the Neurology Commons Repository Citation Schaefer, Kellie A.; Toral, Marcus A.; Velez, Gabriel; Cox, Allison J.; Baker, Sheila A.; Borcherding, Nicholas C.; Colgan, Diana F.; Bondada, Vimala; Mashburn, Charles B.; Yu, Chen Guang; Geddes, James W.; Tsang, Stephen H.; Bassuk, Alexander G.; and Mahajan, Vinit B., "Calpain-5 Expression in the Retina Localizes to Photoreceptor Synapses" (2016). Spinal Cord and Brain Injury Research Center Faculty Publications. 12. https://uknowledge.uky.edu/scobirc_facpub/12 This Article is brought to you for free and open access by the Spinal Cord and Brain Injury Research at UKnowledge. It has been accepted for inclusion in Spinal Cord and Brain Injury Research Center Faculty Publications by an authorized administrator of UKnowledge. For more information, please contact [email protected]. Authors Kellie A. Schaefer, Marcus A. Toral, Gabriel Velez, Allison J. Cox, Sheila A. Baker, Nicholas C. Borcherding, Diana F. Colgan, Vimala Bondada, Charles B. Mashburn, Chen Guang Yu, James W. Geddes, Stephen H. Tsang, Alexander G.
    [Show full text]
  • A Genomic Analysis of Rat Proteases and Protease Inhibitors
    A genomic analysis of rat proteases and protease inhibitors Xose S. Puente and Carlos López-Otín Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Oncología, Universidad de Oviedo, 33006-Oviedo, Spain Send correspondence to: Carlos López-Otín Departamento de Bioquímica y Biología Molecular Facultad de Medicina, Universidad de Oviedo 33006 Oviedo-SPAIN Tel. 34-985-104201; Fax: 34-985-103564 E-mail: [email protected] Proteases perform fundamental roles in multiple biological processes and are associated with a growing number of pathological conditions that involve abnormal or deficient functions of these enzymes. The availability of the rat genome sequence has opened the possibility to perform a global analysis of the complete protease repertoire or degradome of this model organism. The rat degradome consists of at least 626 proteases and homologs, which are distributed into five catalytic classes: 24 aspartic, 160 cysteine, 192 metallo, 221 serine, and 29 threonine proteases. Overall, this distribution is similar to that of the mouse degradome, but significatively more complex than that corresponding to the human degradome composed of 561 proteases and homologs. This increased complexity of the rat protease complement mainly derives from the expansion of several gene families including placental cathepsins, testases, kallikreins and hematopoietic serine proteases, involved in reproductive or immunological functions. These protease families have also evolved differently in the rat and mouse genomes and may contribute to explain some functional differences between these two closely related species. Likewise, genomic analysis of rat protease inhibitors has shown some differences with the mouse protease inhibitor complement and the marked expansion of families of cysteine and serine protease inhibitors in rat and mouse with respect to human.
    [Show full text]
  • Comprehensive Analysis of the Prognostic Value and Immune in Ltration of Calpains in Pancreatic Cancer
    Comprehensive Analysis of the Prognostic Value and Immune Inltration of Calpains in Pancreatic Cancer Lan Chuan Aliated Hospital of North Sichuan Medical College https://orcid.org/0000-0002-6101-222X Haoyou Tang Aliated Hospital of North Sichuan Medical College Sheng Liu Aliated Hospital of North Sichuan Medical College Lin Ma Aliated Hospital of North Sichuan Medical College Yifu Hou ( [email protected] ) University of Electronic Science and Technology of China Research Keywords: bioinformatics analysis, calpains, pancreatic cancer, prognosis, immune inltration Posted Date: August 3rd, 2021 DOI: https://doi.org/10.21203/rs.3.rs-716693/v1 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Page 1/30 Abstract Background: Calpains (CAPNs) are intracellular calcium-activated neutral cysteine proteinases that are involved in cancer initiation, progression, and metastasis; however, their role in pancreatic cancer (PC) remains unclear. Methods: We combined data from various mainstream databases (i.e., Oncomine, GEPIA, Kaplan-Meier plotter, cBioPortal, STRING, GeneMANIA, and ssGSEA) and investigated the role of CAPNs in the prognosis of PC and immune cell inltration. Results: Our results showed that CAPN1, 2, 4, 5, 6, 8, 9, 10, and 12 were highly expressed in PC. The expression levels of CAPN1, 5, 8, and 12 were positively correlated with the individual cancer stages. Moreover, the expression levels of CAPN1, 2, 5, and 8 were negatively correlated with the overall survival (OS) and recurrence-free survival (RFS); whereas that of CAPN10 was positively correlated with OS and RFS. We found that CAPN1, 2, 5, and 8 were correlated with tumour-inltrating T follicular helper cells and CAPN10 with tumour-inltrating T helper 2 cells.
    [Show full text]
  • FASEB SRC “Biology of Calpains in Health and Disease” Co-Organizers: James Geddes and Peter Greer July 21-26, 2013, Saxtons
    FASEB SRC “Biology of Calpains in Health and Disease” Co-Organizers: James Geddes and Peter Greer July 21-26, 2013, Saxtons River, Vermont, USA Introduction: 12:00~12:15, July 23 (Tue), 2013 Discussion: 11:30~12:15, July 24 (Wed), 2013 Revised: September 20 (Fri), 2013 Calpain nomenclature Ref: http://www.calpain.net/ Hiro Sorimachi, IGAKUKEN Peter Davies, Queen’s University A brief history of structures of the conventional calpains Present situation: • Two different numbering exist. • “domain I” is too small to be called domain. Proposed domain structure, color, and nomenclature CysPc: calpain-like cysteine protease core motif [cd00044] defined in the conserved domain database (CDD) of National Center for Biotechnology Information (NCBI). Calpain domain nomenclature MIT: microtubule interaction and transport TML: long transmembrane motif SOL SOL: small optic lobes TPR Zf: zinc-finger motif TPR: tetratricopeptide repeats UBA: ubiquitin associated domain PUB: Peptide:N-glycanase/UBA or UBX-containing Calpain subunit name = Gene product name Human gene Chr. location Gene product Aliases Classical? Ubiquitous? Catalytic subunits μ-calpain large subunit (μCL), CAPN1 11q13 CAPN1 ✔ ✔ μCANP/calpain-I large subunit, μ80K m-calpain large subunit (mCL), CAPN2 1q41-q42 CAPN2 ✔ ✔ mCANP/calpain-II large subunit, m80K CAPN3 15q15.1-q21.1 CAPN3 p94, calpain-3, calpain-3a, nCL-1 ✔ CAPN5 11q14 CAPN5 hTRA-3, nCL-3 ✔ CAPN6 Xq23 CAPN6 calpamodulin, CANPX CAPN7 3p24 CAPN7 PalBH ✔ CAPN8 1q41 CAPN8 nCL-2, calpain-8, calpain-8a ✔ CAPN9 1q42.11-q42.3 CAPN9 nCL-4, calpain-9, calpain-9a ✔ CAPN10 2q37.3 CAPN10 calpain-10a (exon 8 is skipped) ✔ CAPN11 6p12 CAPN11 ✔ CAPN12 19q13.2 CAPN12 calpain-12a, calpain-12A ✔ CAPN13 2p22-p21 CAPN13 ✔ ✔ CAPN14 2p23.1-p21 CAPN14 ✔ ✔ CAPN15/SOLH 16p13.3 CAPN15 SOLH ✔ CAPN16/C6orf103 6q24.3 CAPN16 Demi-calpain, C6orf103 ✔ Regulatory subunits CAPNS1 19q13.1 CAPNS1 CANP/calpain small subunit, 30K, css1, CAPN4 n.a.
    [Show full text]
  • Calpains: Diverse Functions but Enigmatic
    ARCHIVES OF Arch Iran Med. April 2018;21(4):170-179 IRANIAN http www.aimjournal.ir MEDICINE Open Review Article Access Calpains: Diverse Functions but Enigmatic Masoumeh Hosseini, MSc1; Hossein Najmabadi, PhD1*; Kimia Kahrizi, MD1* 1Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran Abstract Calpains are a group of non-lysosomal Ca2+-dependent cysteine proteases with numerous substrates. Calpains have been identified in almost all eukaryotes and bacteria but not in archaebacteria. In the human genome, this group of enzymes has 15 isoforms and is present ubiquitously and demonstrates tissue-specific patterns of expression. Calpains are involved in different physiological and pathological processes such as cell proliferation, migration, invasion, apoptosis and signal transduction and their roles in various disorders have been reported. In this review, functions of calpains, their substrates, their mechanism of regulation and their involvement in diseases have been summarized. Keywords: Calpains, Disorders, Physiological processes, Pathological processes Cite this article as: Hosseini M, Najmabadi H, Kahrizi K. Calpains: diverse functions but enigmatic. Arch Iran Med. 2018;21(4):170– 179. Received: October 23, 2017, Accepted: January 10, 2018, ePublished: April 1, 2018 Introduction and catalytically active sites, including Cys105, His262 and Calpains are a well-conserved group of cysteine Asn286, are conserved in the calpain superfamily. Upon proteases that are involved in some Ca2+-dependent
    [Show full text]
  • Impact Objectives
    Impact Objectives • Develop a better understanding of the molecular mechanisms of calpainopathies by investigating the physiological functions of calpains • Clarify the physiological functions of calpains • Delve deeper into the complexities of calpain molecules as a means of ultimately developing effective drugs and therapies for calpain-related diseases Insights into the complex world of calpains The CALPAIN project is investigating the role of calpains in basic cellular functioning and disease development. Here Dr Hiroyuki Sorimachi discusses his ongoing research and addresses uncertainties around calpains Could you give a Some calpain substrate proteins play on several disease symptoms. Many actions brief explanation important roles in cytoskeletal remodelling, of calpains have been left in a black box. It of what a calpain cell growth, signal transductions for cell cycle is our role to understand and decrease the is and the regulation and stress responses (adaptation). contents of such a black box. background and key For example, it has been suggested CAPN3 is goals behind the involved in stress responses to boost muscle In line with this, the principle of our project CALPAIN project? adaption, and malfunction of CAPN3 by allows us to study calpains as a family of genetic mutation causes muscular dystrophy. protease, providing us with the general A calpain is an intracellular Ca2+-dependent Another example is Eosinophilic oesophagitis, impression. Since some calpain species have protease and is involved in diverse aspects caused by a deficiency of CAPN14, which diverged structures and/or functions, an of cellular functions. Calpain homologs regulates immune response in esophagus. important finding may come from a different exist in almost all eukaryotes and constitute In addition, our study using KO (knockout) direction.
    [Show full text]