{"id":2,"date":"2017-09-06T09:39:47","date_gmt":"2017-09-06T08:39:47","guid":{"rendered":"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/rlw\/?page_id=2"},"modified":"2019-05-09T09:24:36","modified_gmt":"2019-05-09T08:24:36","slug":"home","status":"publish","type":"page","link":"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/rlw\/","title":{"rendered":"Welcome"},"content":{"rendered":"<p class=\"paragraphstyle3\"><span class=\"style1\">Most receptor-mediated signal transduction pathways in mammalian cells involve enzymes that generate either soluble or membrane-resident second messengers by modifying phospholipids present in cell membranes. These enzymes are activated in response to a variety of cellular signals such as hormones, cytokines and neurotransmitters.<\/span><\/p>\n<p class=\"paragraphstyle3\"><span class=\"style1\">We are trying to develop a detailed structural understanding of the network of interacting pathways involved in phospholipid signalling. Our current efforts focus on phosphoinositide 3-kinases (PI3Ks) and a group of protein kinases with catalytic domains related to PI3Ks (PIKKs), including mTOR, ATM and ATR. Due to the frequent mutation of these enzymes in human cancers, a structural understanding of the complexes that they make with their regulators is important for drug development.<\/span><\/p>\n<p class=\"paragraphstyle3\"><span class=\"style1\">In addition to X-ray crystallography, electron cryo-microscopy, hydrogen\/deuterium exchange mass spectrometry (HDX-MS), and other biophysical methods, we are reconstituting the PI3Ks and PIKKs in vitro with membranes and small G proteins that regulate the complexes. These reconstituted systems give us a clear understanding of the kinetic consequences of structural variants of the enzymes, and they have enabled us to develop high-throughput screens for drug discovery that better mimic the biological processes in which the enzymes participate.<\/span><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Most receptor-mediated signal transduction pathways in mammalian cells involve enzymes that generate either soluble or membrane-resident second messengers by modifying phospholipids present in cell membranes. These enzymes are activated in response to a variety of cellular signals such as hormones, cytokines and neurotransmitters. We are trying to develop a detailed structural understanding of the network [&hellip;]<\/p>\n","protected":false},"author":11,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"open","template":"","meta":{"_genesis_hide_title":false,"_genesis_hide_breadcrumbs":false,"_genesis_hide_singular_image":false,"_genesis_hide_footer_widgets":false,"_genesis_custom_body_class":"","_genesis_custom_post_class":"","_genesis_layout":"","footnotes":""},"class_list":{"0":"post-2","1":"page","2":"type-page","3":"status-publish","5":"entry"},"_links":{"self":[{"href":"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/rlw\/wp-json\/wp\/v2\/pages\/2","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/rlw\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/rlw\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/rlw\/wp-json\/wp\/v2\/users\/11"}],"replies":[{"embeddable":true,"href":"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/rlw\/wp-json\/wp\/v2\/comments?post=2"}],"version-history":[{"count":2,"href":"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/rlw\/wp-json\/wp\/v2\/pages\/2\/revisions"}],"predecessor-version":[{"id":179,"href":"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/rlw\/wp-json\/wp\/v2\/pages\/2\/revisions\/179"}],"wp:attachment":[{"href":"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/rlw\/wp-json\/wp\/v2\/media?parent=2"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}