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DESCRIPTION:Navigating protein fitness landscapes in multiple dimensions\n
 \nChristian Landry\, Université Laval\n	Tuesday February 13\, 12-1pm\n	Zoom 
 Link: https://mcgill.zoom.us/j/86855481591\n	In Person: 550 Sherbrooke\, Ro
 om 189\n	\n	Abstract: Proteins could have as many fitness landscapes as they
  have functions. The relationship between mutations and the performance of
  any two functions could be positively or negatively correlated\, making e
 volution on one landscape contingent on evolution on the other. Understand
 ing the evolution of proteins\, therefore\, requires that we characterize 
 how mutations affect the multiple dimensions of the landscapes of protein 
 functions. Here\, I will share our recent work on the deep mutational scan
 ning of two drug-resistance enzymes in which we examine more than one dime
 nsion at a time. In one project\, we examine the trade-off between resista
 nce to an antifungal drug and activity on the canonical substrate of the d
 rug target. We show that the trade-off between the two functions is very s
 teep and shaped by the difference in drug resistance and nutrient use dose
 -response functions. The two fitness functions are nearly perfectly negati
 vely correlated\, meaning no single mutation can lead to resistance while 
 maintaining growth in conditions that require this enzyme. In the second p
 roject\, we examine how expression level affects the fitness landscape of 
 an antibiotic resistance protein. By measuring the effect of all single mu
 tations at optimal and several suboptimal expression levels\, we show that
  optimal expression can mask the effects of many deleterious mutations on 
 enzyme function. Surprisingly\, some beneficial mutations also appear to b
 e masked at optimal expression levels. Protein expression level is\, there
 fore\, a critical factor shaping the fitness landscape of proteins. These 
 two studies illuminate complex protein evolution in heterogeneous growth a
 nd cellular environments.\n
DTSTART:20240213T170000Z
DTEND:20240213T180000Z
SUMMARY:QLS Seminar Series - Christian Landry
URL:/qls/channels/event/qls-seminar-series-christian-l
 andry-354494
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