Media Releases

University of Toronto chemistry technology promises more effective prescription drug therapies

May 5, 2011

TORONTO, ON – Sci­en­tists at the Uni­ver­si­ty of Toron­to, Stan­ford and Colum­bia Uni­ver­si­ties have devel­oped a way to mea­sure the action and func­tion of can­di­date pre­scrip­tion drugs on human cells, includ­ing the response of indi­vid­ual cells, more quick­ly and on a larg­er scale than ever before.

The researchers say their “mass cytom­e­try” tech­nol­o­gy has the poten­tial to trans­form the under­stand­ing of a vari­ety of dis­eases and bio­log­ic actions, and will pro­vide a bet­ter tool to under­stand how a healthy cell becomes dis­eased. Clar­i­fy­ing the under­ly­ing bio­chem­istry of cells may enable ear­li­er detec­tion of ill­ness and ulti­mate­ly advance per­son­al­ized med­i­cine, notably for can­cer and HIV treat­ments, by offer­ing more and less aggres­sive options for treat­ment.

“We’ve shown that drug response is spe­cif­ic to cer­tain sub-pop­u­la­tions of cells, and gained insight into the sig­nal­ing cas­cade that defines that response” says Scott Tan­ner of U of T’s Depart­ment of Chem­istry, who led the devel­op­ment of the tech­nol­o­gy used in research to be pub­lished this week in Sci­ence. “We’ve also shown that a drug can acti­vate or sup­press mul­ti­ple response path­ways simul­ta­ne­ous­ly, and that these respons­es are mod­i­fied when a com­bi­na­tion of drugs are admin­is­tered.”

“Togeth­er, this sug­gests that the tech­nol­o­gy will be of sig­nif­i­cant val­ue in the devel­op­ment and val­i­da­tion of ratio­nal drugs to tar­get par­tic­u­lar pathogens – a quan­tum step towards the pro­vi­sion of per­son­al­ized med­i­cine,” says Tan­ner.

Mass cytom­e­try allows simul­ta­ne­ous mea­sure­ment of as many as 100 bio­mark­ers – spe­cif­ic phys­i­cal traits of cells used to mea­sure or indi­cate the effects or progress of a dis­ease, ill­ness, or con­di­tion – in sin­gle cells, at 1000 cells per sec­ond. It applies the ana­lyt­i­cal capa­bil­i­ties of atom­ic mass spec­trom­e­try – used to mea­sure the num­ber and type of atoms that com­prise a sam­ple – to the tech­nique of flow cytom­e­try, which is a method of exam­in­ing thou­sands of micro­scop­ic par­ti­cles per sec­ond by sus­pend­ing them in a stream of flu­id or gas and pass­ing them through an elec­tron­ic detec­tion appa­ra­tus. The two very dis­parate dis­ci­plines pre­vi­ous­ly had no rea­son to be com­bined.

The U of T sci­en­tists devel­oped the chem­istry and meth­ods of attach­ing the met­al atoms nec­es­sary for the detec­tion of the van­ish­ing­ly rare bio­mol­e­cules of inter­est at the indi­vid­ual cell lev­el, where per­son­al ther­a­peu­tic response is defined. They also devel­oped a unique instru­ment to simul­ta­ne­ous­ly mea­sure a large num­ber of these diag­nos­tic sig­nals for indi­vid­ual cells at a high analy­sis rate. Gar­ry Nolan, a pro­fes­sor of micro­bi­ol­o­gy and immunol­o­gy at Stan­ford Uni­ver­si­ty and lead inves­ti­ga­tor of the research pre­sent­ed in this paper, adapt­ed and expand­ed his ear­li­er work in flow cytom­e­try to take advan­tage of the much high­er pow­er that mass cytom­e­try pro­vides.

Nolan and his col­leagues at Stan­ford, with col­lab­o­ra­tors at Colum­bia, used the U of T tech­nol­o­gy to mon­i­tor 34 dif­fer­ent sub­stances found inside and on the sur­face of dif­fer­ent cell types pro­duced in human bone mar­row, the place where all immune and blood cells, as well as blood dis­or­ders such as leukemia, orig­i­nate. They were able not only to cor­rect­ly cat­e­go­rize over a dozen dif­fer­ent immune cell types but, at the same time, to peer inside the cells and learn how var­i­ous inter­nal process­es dif­fered from one cell type to the next. “We can tell not only what kind of cell it is but what it’s think­ing, and what it may become,” says Nolan.

The find­ings are pre­sent­ed in a paper titled “Sin­gle-Cell Mass Cytom­e­try of Dif­fer­en­tial Immune and Drug Respons­es Across a Human Hematopoi­et­ic Con­tin­u­um”, to be pub­lished May 6 in Sci­ence. The tech­nol­o­gy devel­oped by Tan­ner and his asso­ciates is being brought to mar­ket by DVS Sci­ences Inc., a U of T spin-off of which Tan­ner is pres­i­dent and CEO.

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The prin­ci­pal inves­ti­ga­tor for the devel­op­ment of the tech­nol­o­gy used in this work is Scott Tan­ner, Depart­ment of Chem­istry at the Uni­ver­si­ty of Toron­to. The instru­ment tech­nol­o­gy was invent­ed and devel­oped by the Tan­ner group in Chem­istry (prin­ci­pal­ly by Tan­ner, Olga Ornatsky, Dmit­ry Ban­dura and Vladimir Bara­nov) and the met­al-label­ing reagents were devel­oped togeth­er with col­lab­o­ra­tors in the Chem­istry research groups of Mitch Win­nik (notably Xudong Lou) and Mark Nitz. Addi­tion­al sup­port came from Genome Cana­da via the Ontario Genomics Insti­tute, the Ontario Insti­tute for Can­cer Research and the Ontario Research Fund.

The tech­nol­o­gy devel­op­ment project was enabled by the gen­er­ous col­lab­o­ra­tion of Dr. John Dick of the Uni­ver­si­ty Health Net­work.

The prin­ci­pal inves­ti­ga­tor for the appli­ca­tion pre­sent­ed in the paper is Gar­ry Nolan of Stan­ford Uni­ver­si­ty. The lead authors are Sean Ben­dall and Erin Simonds, mem­bers of the Nolan team.

 

For more infor­ma­tion, please con­tact:

 

Scott Tan­ner
Depart­ment of Chem­istry
Uni­ver­si­ty of Toron­to
905–513-1704 ext 5921 (office)
289–221-3423 (cell)
sd.tanner@utoronto.ca

 

Sean Bet­tam
Com­mu­ni­ca­tions, Fac­ul­ty of Arts & Sci­ence
Uni­ver­si­ty of Toron­to
416–946-7950
s.bettam@utoronto.ca