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James Friesen, Co-Founder of Donnelly Centre | Donnelly Centre for Cellular and Biomolecular Research
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40px" width="900" height="600"/> <source srcset="/sites/default/files/styles/landscape_3_2_200/public/Friesen%20photo%20scan.jpg?itok=8Amny_sc 200w, /sites/default/files/styles/landscape_3_2_400/public/Friesen%20photo%20scan.jpg?itok=GyFBYL6E 400w, /sites/default/files/styles/landscape_3_2_600/public/Friesen%20photo%20scan.jpg?itok=c2RHmpHW 600w, /sites/default/files/styles/landscape_3_2_860/public/Friesen%20photo%20scan.jpg?itok=Y396dWod 900w, /sites/default/files/styles/landscape_3_2_1200/public/Friesen%20photo%20scan.jpg?itok=rwg4ScR- 1200w, /sites/default/files/styles/landscape_3_2_1500/public/Friesen%20photo%20scan.jpg?itok=-gg_OYff 1500w, /sites/default/files/styles/landscape_3_2_1800/public/Friesen%20photo%20scan.jpg?itok=UxXPMPQD 1800w, /sites/default/files/styles/landscape_3_2_2000/public/Friesen%20photo%20scan.jpg?itok=BnFbsY4S 2000w, /sites/default/files/styles/landscape_3_2_2500/public/Friesen%20photo%20scan.jpg?itok=TTBcESrt 2500w, /sites/default/files/styles/landscape_3_2_2800/public/Friesen%20photo%20scan.jpg?itok=vVwk8Ah8 2800w, /sites/default/files/styles/landscape_3_2_3000/public/Friesen%20photo%20scan.jpg?itok=L_GnVSwk 3000w" type="image/jpeg" sizes="(min-width:1280px) 280px, (min-width:600px) 20vw, 100vw - 40px" width="900" height="600"/> <img width="900" height="600" srcset="/sites/default/files/styles/landscape_3_2_200/public/Friesen%20photo%20scan.jpg?itok=8Amny_sc 200w, /sites/default/files/styles/landscape_3_2_400/public/Friesen%20photo%20scan.jpg?itok=GyFBYL6E 400w, /sites/default/files/styles/landscape_3_2_600/public/Friesen%20photo%20scan.jpg?itok=c2RHmpHW 600w, /sites/default/files/styles/landscape_3_2_860/public/Friesen%20photo%20scan.jpg?itok=Y396dWod 900w, /sites/default/files/styles/landscape_3_2_1200/public/Friesen%20photo%20scan.jpg?itok=rwg4ScR- 1200w, /sites/default/files/styles/landscape_3_2_1500/public/Friesen%20photo%20scan.jpg?itok=-gg_OYff 1500w, /sites/default/files/styles/landscape_3_2_1800/public/Friesen%20photo%20scan.jpg?itok=UxXPMPQD 1800w, /sites/default/files/styles/landscape_3_2_2000/public/Friesen%20photo%20scan.jpg?itok=BnFbsY4S 2000w, /sites/default/files/styles/landscape_3_2_2500/public/Friesen%20photo%20scan.jpg?itok=TTBcESrt 2500w, /sites/default/files/styles/landscape_3_2_2800/public/Friesen%20photo%20scan.jpg?itok=vVwk8Ah8 2800w, /sites/default/files/styles/landscape_3_2_3000/public/Friesen%20photo%20scan.jpg?itok=L_GnVSwk 3000w" sizes="(min-width:1280px) 280px, (min-width:600px) 20vw, 100vw - 40px" src="/sites/default/files/styles/landscape_3_2_600/public/Friesen%20photo%20scan.jpg?itok=c2RHmpHW" loading="lazy" typeof="foaf:Image" /> </picture> </div> </div> <div class="m-text-image--right__text"> <div class="m-text-image__body s-wysiwyg"> <div class="s-wysiwyg"><p>James Friesen was BBDMR Chair (1996-2004) and former Director of Research at the Hospital for Sick Children (1987-1995) and Chair of the Department of Medical Genetics (1981-1987), now known as Molecular Genetics. Along with Professor Cecil Yip, he co-founded the Donnelly Centre in 2002 and served as its interim-director until 2004. He received an M.A. from the University of Saskatchewan and a PhD from the University of Toronto before obtaining postdoctoral training at the University of Copenhagen in Denmark.</p></div> </div> </div> </div> </div> <div class="paragraph--published"> <div class="m-text"> <div class="m-text__content s-wysiwyg"> <div class="s-wysiwyg"><h2>Dr. Friesen's research overview</h2> <p>The most fun I had in my research career was in the early days. I did a postdoc at the Microbiology Institute, University of Copenhagen, and continued off-and-on collaboration with scientists from there, especially <strong>Niels Fiil</strong>. The atmosphere in molecular genetics in those days was rather similar to today: rapid and exciting developments, new gene technologies (restriction enzymes, based on bacterial defence mechanisms—shades of CRISPR; DNA sequencing; gene cloning), and a feeling that we were at the beginning of something big and open-ended.</p> <p>We were studying growth regulation, and more particularly synthesis regulation of ribosomal components in <em>E. coli</em>, at that time the work-horse of molecular genetics. Prokaryotes don't have a nuclear membrane, so an important aspect of molecular regulation is the possibility of nearly direct coupling of transcription and translation control mechanisms. This proved to be the case for ribosomal components through the so-called “stringent response”, in which ribosomal RNA synthesis was shut down during nutritional deprivation. The discovery by <strong><a href="https://irp.nih.gov/pi/charles-cashel" rel="noopener noreferrer" target="_blank">Mike Cashel</a> </strong>and <strong><a href="http://www.gs.washington.edu/faculty/gallant.htm" rel="noopener noreferrer" target="_blank">Jon Gallant</a> </strong>that guanosine tetraphosphate (ppGpp) is an effector of this response and by <a href="https://en.wikipedia.org/wiki/William_A._Haseltine" rel="noopener noreferrer" target="_blank"><strong>Bill Haseltine</strong></a> and <strong>Ricardo Block</strong> that it was made on “idling” ribosomes deprived of amino acids, completed the regulatory link between ribosomes and RNA polymerase. We began hunting for mutants of <em>E. coli</em> that escaped this so-called “stringent” growth response in order to find new ribosomal components involved in ppGpp synthesis and/or degradation. Our ppGpp assays were done using 2-D thin-layer chromatography 32P orthophosphate in open plastic dish pans (Ah, for the good old days).</p></div> </div> </div> </div> <div class="paragraph--published"> <blockquote class="m-quote m-quote--default"> <div class="m-quote__icon"> <div class="a-icon--sml"> <i class="fas fa-quote-left" data-fa-transform="" data-fa-mask="" ></i> </div> </div> <div class="m-quote__text-wrapper--default"> <div class="m-quote__body--default"> <div class="s-wysiwyg">The atmosphere in molecular genetics in those days was rather similar to today: rapid and exciting developments, new gene technologies, and a feeling that we were at the beginning of something big and open-ended</div> </div> <div class="m-quote__quote__source"> James Friesen, Professor Emeritus </div> </div> </blockquote> </div> <div class="paragraph--published"> <div class="m-text"> <div class="m-text__content s-wysiwyg"> <div class="s-wysiwyg"><p>In parallel, we began studying the biosynthetic regulation of the structural genes for ribosomal proteins and translation-factors. For this we needed to identify the genes coding for individual ribosomal proteins and rRNA, determine their genomic position in relation to each other (remember operons?) and then study their biosynthetic regulation. Our first gene cloning was done Nature's way using λ specialized transducing phages, selecting for nearby nutritional markers and then screening for the presence of ribosomal genes. When restriction enzymes became available (at first we had to make our own crude extracts for some of them) we could cut up the <em>E.coli </em>genome and clone on to plasmids, again selecting for nearby markers. However, subsequent localization of genomic regulatory elements and operons, and determination of operon gene-order was much easier using this method. Sequencing by hand using the <a href="https://en.wikipedia.org/wiki/Sanger_sequencing" target="_blank">Sanger method</a> verified the gene orders and also was a fast short-cut to finding the amino acid sequence of ribosomal proteins as a first step to determining their function. This was thought to be important because this era was decades before it was shown that RNA was the catalytic agent, rather than proteins; at the time everybody thought it was the other way around. We showed (as did <a href="http://www.asbmb.org/asbmbtoday/201201/Retrospective/Nomura/" target="_blank"><strong>Masayasu Nomura</strong></a>) that ribosomal protein synthesis was controlled by a feedback translational mechanism.</p> <p>As a basis for development of new antibiotics there is a current interest in research on bacterial growth regulation. Every once in a while I see a reference to one of our forty-year-old papers on the subject—quite a thrill.</p> <p>Later on, I switched to yeast and started by isolating genes of the transcription and translation systems. But that's another story.</p> <h3>Select publications:</h3> <p>Friesen JD (1968) A study of the relationship between polyribosomes and messenger RNA in <em>Escherichia coli.</em> <em>J. Mol. Biol. </em>32:183.</p> <p>Friesen JD, Fiil N (1968) Selection of relaxed mutants of <em>E. coli.</em> <em>J. Bacteriol.</em> 95:729.</p> <p>Friesen JD, Fiil NP, Parker J, Haseltine WA (1974) A new relaxed mutant of <em>Escherichia coli </em>with an altered 50s ribosomal subunit. <em>Proc. Natl. Acad. Sci. </em>USA 71:3465.</p> <p>Watson RJ, Parker J, Fiil NP, Flaks JG, Friesen JD (1975) New chromosomal location for structural genes of ribosomal proteins. <em>Proc. Natl. Acad. Sci.</em> USA 72:2765.</p> <p>Friesen JD, Fiil NP, von Meyenburg K (1975) Synthesis and turnover of basal level guanosine tetraphosphate in <em>Escherichia coli. </em> J. Biol. Chem. 250:304.</p> <p>Reeh S, Pedersen S, Friesen JD. <em>Mol Gen Genet.</em> (1976) Dec 22;149(3):279-89. Biosynthetic regulation of individual proteins in relA+ and relA strains of <em>Escherichia coli </em>during amino acid starvation.</p> <p>Parker J, Friesen JD (1980) "Two out of three" codon reading leading to mistranslation in vivo. <em>Mol. Gen. Genet. </em>177:439.</p> <p>Parker J, Pollard JW, Friesen JD, Stanners CP (1978) Stuttering: Mistranslation in mammalian and bacterial cells. <em>Proc. Natl. Acad. Sci.</em> USA. 75:1091.</p> <p>Ingles CJ, Himmelfarb HJ, Shales M, Greenleaf AL, Friesen JD (1984) Identification, molecular cloning and mutagenesis of <em>Saccharomyces cerevisiae</em> RNA Polymerase genes. <em>Proc. Natl. Acad. Sci.</em> USA 81:2157-2161.</p> <p>Mamelak L, Christensen T, Fiil N, Friesen JD, Johnsen M (1984) Alternate mRNA secondary structures as a mechanism of translation-inhibition. In: "Molecular Biology of Bacterial Growth" (M Schaechter, FC Neidhardt, J Ingraham, NO Kjeldgaard, eds.) Jones and Bartlett Published, Inc.</p> <p>Fouser LA, Friesen JD (1987). The effects on mRNA splicing of mutations in the 3' region of the <em>S. cerevisiae</em> actin intron. <em>Mol. Cell. Biol</em>. 7:225-230.</p> <p>Himmelfarb HJ, Simpson EM, Friesen JD (1987). Isolation and characterization of temperature-sensitive RNA polymerase II mutants of <em>Saccharomyces cerevisiae. Mol. Cell. Biol.</em> 7: 2155-2164.</p> <p>Climie SC, Friesen JD (1988). A region of mRNA secondary structure is necessary for feedback regulation of the L10 ribosomal protein of <em>Escherichia coli. J. Mol. Biol</em>. 98:371-381.</p> <p>Climie SC, Friesen JD (1988). In vivo and in vitro structural analysis of the Escherichia coli rplJ mRNA leader: protection by bound L10-L7/L12. <em>J. Biol. Chem</em>. 263:15166-15175.</p> <p>Xu Y, Petersen-Bjorn S, Friesen JD. (1990) The PRP4 (RNA4) protein of <em>Saccharomyces cerevisiae</em> is associated with the 5' portion of the U4 small nuclear RNA. <em>Mol. Cell. Biol</em>. 10: 1217-1225.</p> <p>Fouser LA, Friesen JD (1987). The effects on mRNA splicing of mutations in the 3' region of the <em>S. cerevisiae</em> actin intron. <em>Mol. Cell. Biol.</em> 7:225-230.</p> <p>Archambault J, Schappert K, Friesen JD. (1991) A suppressor for an RNA Polymerase II mutant of <em>Saccharomyces cerevisiae</em> encodes a subunit common to RNA Polymerase I, II and III. <em>Mol. Cell Biol.</em> 10: 6123-6131.</p> <p>Archambault J1, Friesen JD. (1993) Genetics of eukaryotic RNA polymerases I, II, and III. Microbiol. Rev. 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Best Postdoctoral Fellowship</a> </li> <li class="m-menu-mobile__item--level-2"> <a href="/donnelly-centre-home-fellowship" class="m-menu-mobile__link--level-2" data-drupal-link-system-path="node/1353">Donnelly Centre Home Fellowship</a> </li> <li class="m-menu-mobile__item--level-2"> <a href="/donnelly-centre-research-excellence-award" class="m-menu-mobile__link--level-2" data-drupal-link-system-path="node/356">Donnelly Centre Research Excellence Award</a> </li> </ul> </li> <li class="menu-firstchild m-menu-mobile__item--level-1 has-submenu"> <a href="/news" class="m-menu-mobile__link--level-1 is-toggle">News</a> <ul class="m-menu-mobile__list--level-2"> <li class="m-menu-mobile__item--level-2"> <a href="/news" class="m-menu-mobile__link--level-2" data-drupal-link-system-path="node/381">News</a> </li> <li class="m-menu-mobile__item--level-2"> <a href="/donnelly-centre-magazine" title="" class="m-menu-mobile__link--level-2" data-drupal-link-system-path="node/374">Donnelly Centre Magazine</a> </li> <li class="m-menu-mobile__item--level-2"> <a href="/annual-reports" class="m-menu-mobile__link--level-2" data-drupal-link-system-path="node/400">Annual Reports</a> </li> <li class="m-menu-mobile__item--level-2 has-submenu"> <a href="/donnelly-media" class="m-menu-mobile__link--level-2 is-toggle" data-drupal-link-system-path="node/316">Donnelly in the Media</a> <ul class="m-menu-mobile__list--level-3"> <li class="m-menu-mobile__item--level-3"> <a href="/media-archive-2008-2020" class="m-menu-mobile__link--level-3" data-drupal-link-system-path="node/426">In the Media Archive (2008-2020)</a> </li> </ul> </li> </ul> </li> <li class="menu-firstchild m-menu-mobile__item--level-1 has-submenu"> <a href="/current-opportunities" class="m-menu-mobile__link--level-1 is-toggle">Careers</a> <ul class="m-menu-mobile__list--level-2"> <li class="m-menu-mobile__item--level-2"> <a href="/current-opportunities" class="m-menu-mobile__link--level-2" data-drupal-link-system-path="node/283">Current Opportunities</a> </li> <li class="m-menu-mobile__item--level-2"> <a href="/working-and-living-toronto" title="" class="m-menu-mobile__link--level-2" data-drupal-link-system-path="node/299">Working and Living in Toronto</a> </li> </ul> </li> <li class="m-menu-mobile__item--level-1 has-submenu"> <a href="/events" class="m-menu-mobile__link--level-1 is-toggle" data-drupal-link-system-path="node/1249">Events</a> <ul class="m-menu-mobile__list--level-2"> <li class="m-menu-mobile__item--level-2"> <a href="/events" class="m-menu-mobile__link--level-2" data-drupal-link-system-path="node/1249">Events</a> </li> <li class="m-menu-mobile__item--level-2"> <a href="/postdoctoral-fellow-and-research-associate-seminars" class="m-menu-mobile__link--level-2" data-drupal-link-system-path="node/323">Postdoctoral Fellow and Research Associate Seminars</a> </li> </ul> </li> <li class="menu-firstchild m-menu-mobile__item--level-1 is-active has-submenu"> <a href="/welcome-director" class="m-menu-mobile__link--level-1 is-toggle">About Us</a> <ul class="m-menu-mobile__list--level-2"> <li class="m-menu-mobile__item--level-2"> <a href="/welcome-director" class="m-menu-mobile__link--level-2" data-drupal-link-system-path="node/455">Director's Welcome Message</a> </li> <li class="m-menu-mobile__item--level-2"> <a href="/terrence-j-donnelly" class="m-menu-mobile__link--level-2" data-drupal-link-system-path="node/304">Terrence J. Donnelly</a> </li> <li class="m-menu-mobile__item--level-2 is-active has-submenu"> <a href="/built-21st-century-science" class="m-menu-mobile__link--level-2 is-toggle" data-drupal-link-system-path="node/285">History of the Donnelly Centre</a> <ul class="m-menu-mobile__list--level-3"> <li class="m-menu-mobile__item--level-3"> <a href="/banting-and-best-department-medical-research-timeline" class="m-menu-mobile__link--level-3" data-drupal-link-system-path="node/347">Get to know our history through this interactive timeline</a> </li> <li class="m-menu-mobile__item--level-3"> <a href="/banting-and-best-department-medical-research" class="m-menu-mobile__link--level-3" data-drupal-link-system-path="node/344">Banting and Best Department of Medical Research</a> </li> <li class="m-menu-mobile__item--level-3"> <a href="/brenda-andrews-founding-director-donnelly-centre" class="m-menu-mobile__link--level-3" data-drupal-link-system-path="node/476">Brenda Andrews, Founding Director of Donnelly Centre</a> </li> <li class="m-menu-mobile__item--level-3 is-active"> <a href="/james-friesen-co-founder-donnelly-centre" class="m-menu-mobile__link--level-3 is-active" data-drupal-link-system-path="node/348" aria-current="page">James Friesen, Co-Founder of Donnelly Centre</a> </li> <li class="m-menu-mobile__item--level-3"> <a href="/cecil-yip-co-founder-donnelly-centre" class="m-menu-mobile__link--level-3" data-drupal-link-system-path="node/346">Cecil Yip, Co-Founder of Donnelly Centre</a> </li> </ul> </li> <li class="m-menu-mobile__item--level-2"> <a href="/staff" class="m-menu-mobile__link--level-2" data-drupal-link-system-path="node/305">Staff</a> </li> <li class="m-menu-mobile__item--level-2"> <a href="/image-gallery" class="m-menu-mobile__link--level-2" data-drupal-link-system-path="node/328">Image Gallery</a> </li> <li class="m-menu-mobile__item--level-2"> <a href="/contact-us" class="m-menu-mobile__link--level-2" data-drupal-link-system-path="node/311">Contact Us</a> </li> </ul> </li> <div id="menu-mobile-header-content"> <div class="m-menu-mobile__header-content"> </div> </div> </ul> </nav> </nav> </div> <script>window.dataLayer = window.dataLayer || []; window.dataLayer.push({"drupalLanguage":"en","drupalCountry":null,"siteName":"Donnelly Centre for Cellular and Biomolecular Research","entityName":"migrate","entityType":"node","entityBundle":"ed_page","entityId":"348","entityTitle":"James Friesen, Co-Founder of Donnelly Centre","userUid":0,"breadcrumbLevel1":"About Us","breadcrumbLevel2":"History of the Donnelly Centre","breadcrumbLevel3":"James Friesen, Co-Founder of Donnelly Centre"});</script> <link rel="stylesheet" href="https://use.typekit.net/zls1oah.css"> <script type="application/json" data-drupal-selector="drupal-settings-json">{"path":{"baseUrl":"\/","pathPrefix":"","currentPath":"node\/348","currentPathIsAdmin":false,"isFront":false,"currentLanguage":"en"},"pluralDelimiter":"\u0003","suppressDeprecationErrors":true,"ajaxPageState":{"libraries":"eJx9kFEKAyEQQy8keiSJOlWpzoijXfb2XUqhpR_9eySBhITtwraxULzTNBEX3drW4j5oO_E2ceuS7pF6ZddReRGDI3mWVSOpSVhoOGm6QAWPKlPNTXjhIJVO7outPrINE5z-R1RaTSaL5EYejHZeVep-BTMwkSdGUZfmHmj2o9jNY4dWtVAyeuqi7gKUzEFhIF6dm6_pVdinKSPJwX8s__ri7ecmAe0Jwbd-_A","theme":"webpac","theme_token":null},"ajaxTrustedUrl":[],"bu":{"_core":{"default_config_hash":"AblkqYHezKA1TuKStbuiQqvACikY5ElI-bHxMy-C25U"},"notify_ie":11,"notify_firefox":-2,"notify_opera":-2,"notify_safari":-2,"notify_chrome":-2,"insecure":false,"unsupported":false,"mobile":false,"visibility_type":"hide","visibility_pages":"admin\/*","source":"\/\/browser-update.org\/update.min.js","show_source":"","position":"top","text_override":"","reminder":4380,"reminder_closed":4380,"new_window":true,"url":"","no_close":false,"test_mode":false},"dataLayer":{"defaultLang":"en","languages":{"en":{"id":"en","name":"English","direction":"ltr","weight":0}}},"google_analytics":{"account":"UA-34496632-11","trackOutbound":true,"trackMailto":true,"trackTel":true,"trackDownload":true,"trackDownloadExtensions":"7z|aac|arc|arj|asf|asx|avi|bin|csv|doc(x|m)?|dot(x|m)?|exe|flv|gif|gz|gzip|hqx|jar|jpe?g|js|mp(2|3|4|e?g)|mov(ie)?|msi|msp|pdf|phps|png|ppt(x|m)?|pot(x|m)?|pps(x|m)?|ppam|sld(x|m)?|thmx|qtm?|ra(m|r)?|sea|sit|tar|tgz|torrent|txt|wav|wma|wmv|wpd|xls(x|m|b)?|xlt(x|m)|xlam|xml|z|zip"},"user":{"uid":0,"permissionsHash":"e5117ae9e1952bc666f6f6eded612e9062e3e550f37a6e73234d0ebf81dbff34"}}</script> <script src="/sites/default/files/js/js_vMSEPHDskVi_p9TfdYxNiqFwZ_jUvnuiJNwO6MCW38g.js?scope=footer&delta=0&language=en&theme=webpac&include=eJx9jkEOwyAMBD-E4EnIxg5BdewIQ1B-314qVT3ktjs7h8WZcMayc3lxDwQDBG7uCXmHq1n3sJkOWOx2cPrJ0a8a3aTRo4EdlDxUsyqcQUHu0YqnfxAW4wklVTEE-bbNpn4-NdNM3U6ypQ9TPljnG5FMUo4"></script> </body> </html>