LU, Tim, Engineering Gene Circuits, MIT, April 8, 2019
<p>LU, Tim, Engineering Gene Circuits, MIT, April 8, 2019
This is a 4PM bio. seminar at Clark Aud. at Stanford</p>
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<p>He is an assoc prof at MIT in synthetic bio.</p>
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<p>intro: (<strong>TL = Timothy Lu </strong>was born at Stanford!)</p>
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<p>he also has appts in EE, CSD and in Dept of Bio Engr.</p>
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<p>opens with his corporate affiliations. (two companies)</p>
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<p>non-invasive sensors for the gut (will discuss)</p>
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<p>2nd: <strong>DOMINO</strong>.. platform for DNA-based memory and sequential compuuting, etc.</p>
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<p>DNA reading/ writing is cheaper, faster, easier (as per Moore's Law)</p>
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<p>he shows categories of apps for synthetic bio.</p>
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<p>computing and memory in cells;</p>
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<p>living materials;</p>
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<p>next-gen biomanufac... doses of biologics eg on the moon</p>
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<p>infectious diseases (won't discuss today)</p>
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<p>microbiome engr inside us...</p>
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<p> first topic *</p>
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<p><strong>Gene circuits for in vivo gut monitoring of microbiome or other analytes.</strong></p>
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<p>want to add a strain, eg, that does something... eg a <strong>new sensor</strong>...</p>
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<p>or subtractive (to knock out a bad strain)</p>
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<p>look eg for <strong>bleeding, cancer biomarkers, inflammation, infection</strong></p>
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<p>sense it and report it....</p>
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<p>swallow a chip inside a capsule!!! and it works with that bacteria to report what it's sensing.</p>
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<p>see Mimee, Nadau....</p>
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<p>capsule-sized form factor</p>
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<p>put bacteria onto the chip that has biosensors and chip sends signal to your cellphone
via bluetooth.</p>
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<p>blood sensing bacteria.... reported by luciferase on chip.</p>
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<p>gavage mice with indomethacin to induce bleeding....</p>
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<p>yes, it works. pill is length of about two dimes currently
... we are working to make it smaller.</p>
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<p>low power.... it just transmits once in a while... to bluetooth receive on your phone.</p>
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<p>see <strong>Mimee, Nadeau.. Lu in Science in 2018</strong>.</p>
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<p>trying to miniaturize it.</p>
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<p>want it for <strong>colon cancer or bowel disease.</strong></p>
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<p>can do quorum sensing wiht LuxCDABE.</p>
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<p>Nitric Oxide sensor.... want to get different concentration levels....</p>
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<p>and hook up to memory circuit.</p>
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<p>flips a molecule on and it stays on.</p>
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<p>might also make drugs inside body.</p>
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<p> 2nd topic: DOMINO </p>
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<p>understanding living materials</p>
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<p>DOMINO</p>
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<p><strong>DNA-based ordered memory and iteration network operators.</strong></p>
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<p>DOMINO uses a similar principle as hard drive....</p>
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<p>use a genetic read and write head.</p>
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<p>like a Turing tape....</p>
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<p>use DNA....</p>
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<p>early work used nCas9 for write head.</p>
<p>can do C=> T modification.</p>
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<p>do <strong>DOMINO logic eg A AND B.</strong></p>
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<p>can use this to change conversion of gRNA. (guide RNA)</p>
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<p>adding a TC and IPTG and Arabinose to trigger system.</p>
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<p>want to also<strong> capture sequential events like A AND THEN B.</strong></p>
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<p>and next... temporal DOMINO logic eg</p>
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<p><strong>A AND AFTER TIME X then B...</strong></p>
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<p>can also get associative learning where the weight is expressed by level of GFP...</p>
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<p>3rd topic *</p>
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<p>clinical applications.... therapeutics for human use... eg for cancer.</p>
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<p>viral therapies eg oncolytic therapies... want increased specificity.</p>
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<p>synthetic promoters (only turn on with v specific tumor cells eg)</p>
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<p>use FACS sorting to screen for good promoters eg for specific cancer cells.</p>
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<p>developed using organoid models...</p>
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<p>studied with different breast cancer lines.</p>
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<p>use NGS = next gen seq. and ML = machine learning to screen results.</p>
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<p>also working on glioblastoma eg to distinguish glioblastoma stem-like cells .</p>
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<p>* and also ....</p>
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<p>engineering logic circuits for immunotherapy.</p>
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<p>viral-based immunotherapies for cancer....</p>
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<p>read specifc RNA and then clobber the cell with</p>
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<p>eg four specific therapy pathways....
(I left early to attend MBCT lecture by Tobias Gerstenberg on Causality)</p>
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