New map uncovers the traffic of life in a cell

Led by Pro­fes­sors Bren­da Andrews, Charles Boone, and Jason Mof­fat from the Uni­ver­si­ty of Toronto’s Don­nel­ly Cen­tre, the team built a state-of-the-art auto­mat­ed pipeline to mon­i­tor where pro­teins sit in the cell and to see how they move in response to genet­ic or envi­ron­men­tal per­tur­ba­tions.

The study is pub­lished in today’s issue of Cell, a lead­ing jour­nal in the field.

The detailed data­base of pro­tein loca­tions will be made avail­able, also this month, through G3: Genes|Genomes|Genetics, the offi­cial jour­nal of the Genet­ics Soci­ety of Amer­i­ca, so that any­one can look up loca­tion and move­ment of their protein(s) of inter­est.

As cells do their jobs, such as mak­ing, main­tain­ing and repair­ing our bod­ies, they con­tin­u­ous­ly move pro­teins around. But sci­en­tists under­stand very lit­tle about how this traf­fic occurs inside our cells. This is about to change as the new map, which charts pro­tein move­ment and abun­dance, becomes avail­able. Much as the ship­ping or air­line routes give insights into the state of world econ­o­my, so this new pro­tein map will help sci­en­tists under­stand bet­ter what hap­pens in cells when they are healthy and what goes wrong in a dis­ease.

Pro­teins are prod­ucts of genes and they are respon­si­ble for all the work­ings of the cell.

“A lot of the reg­u­la­tion that hap­pens with­in cells, which is crit­i­cal for the basic func­tion­ing of the human body, influ­ences where indi­vid­ual pro­teins are local­ized and how they move around. It is very impor­tant to under­stand how this reg­u­la­tion hap­pens if we are going to be able to under­stand why cells are healthy and why they are some­times dis­eased,” says Bren­da Andrews, who is also a pro­fes­sor in U of T’s Depart­ment of Mol­e­c­u­lar Genet­ics.

To visu­al­ize and count most of the rough­ly 6000 pro­teins in the cell, researchers col­lect­ed data for mind-bog­gling 20 mil­lion cells. For more than a decade, the sci­en­tists worked close­ly togeth­er with robot­ic engi­neers, who built machines to han­dle the cells, and soft­ware writ­ers who designed arti­fi­cial intel­li­gence-based algo­rithms to process the vast amount of data.

“The rea­son we need to do it on a large scale is because there sim­ply are so many pro­teins,” says Andrews, who uses baker’s yeast as a mod­el to under­stand human cell biol­o­gy.

Yeast cells work in very sim­i­lar ways to human cells but have few­er pro­teins, around a quar­ter the num­ber that exist in more com­plex human cells. This rel­a­tive sim­plic­i­ty has allowed researchers like Andrews and Boone to use yeast to make many fun­da­men­tal insights into how both yeast and human cells work.

Their team not only chart­ed pro­tein move­ment and abun­dance in nor­mal cells, but they also looked at what hap­pen when cells car­ry a muta­tion, which could lead to a genet­ic dis­ease, for exam­ple, or when they are exposed to dif­fer­ent drugs.

“We’ve devel­oped meth­ods that allow sci­en­tists to exam­ine all of pro­teins in the cell and how they change in response to any kind of per­tur­ba­tion,” says Andrews.

Next, the researchers will use this pow­er­ful pipeline to inves­ti­gate how pro­teins move in human cells, such as can­cer cells, to under­stand bet­ter the ori­gin of the dis­ease, but also to search for new treat­ments.

“We want to under­stand how all pro­teins are mov­ing, at a sys­tems lev­el, in can­cer cells upon, say, a treat­ment with a drug or genet­ic per­tur­ba­tion, so that we can iden­ti­fy vul­ner­a­bil­i­ties in can­cer cells, in terms of pro­tein local­iza­tion and abun­dance, and start think­ing about how to best tar­get those changes,” says Mof­fat, also a pro­fes­sor in U of T’s Depart­ment of Mol­e­c­u­lar Genet­ics.

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For more infor­ma­tion:

Erin Howe
Writer/Videographer
Office of Com­mu­ni­ca­tion, Strat­e­gy and Exter­nal Rela­tions
Uni­ver­si­ty of Toron­to, Temer­ty Temer­ty Fac­ul­ty of Med­i­cine
416–946-5266
erin.howe@utoronto.ca