Alek­san­dra Badura 

Title

Use of mul­ti-para­met­ric assays to cap­ture sex- and envi­ron­ment-mod­i­fiers of behav­iour­al phe­no­types in autism mouse models 

Abstract

Cur­rent phe­no­typ­ing approach­es for murine autism mod­els often focus on one select­ed behav­ioral fea­ture, mak­ing the trans­la­tion onto a spec­trum of autis­tic char­ac­ter­is­tics chal­leng­ing. Fur­ther­more, sex and envi­ron­men­tal fac­tors are rarely considered. 

Here, we aimed to cap­ture the full spec­trum of behav­ioral man­i­fes­ta­tions in three autism mouse mod­els to devel­op a “behav­ioral fin­ger­print” that takes envi­ron­men­tal and sex influ­ences under con­sid­er­a­tion. To this end, we employed a wide range of clas­si­cal stan­dard­ized behav­ioral tests; and two mul­ti-para­met­ric behav­ioral assays: the Live Mouse Track­er and Motion Sequenc­ing (MoSeq), on male and female Shank2, Tsc1 and Purk­in­je cell spe­cif­ic-Tsc1 mutant mice raised in stan­dard or enriched environments. 

Our aim was to inte­grate our high dimen­sion­al data into one sin­gle plat­form to clas­si­fy dif­fer­ences in all exper­i­men­tal groups along dimen­sions with max­i­mum dis­crim­i­na­tive pow­er. Mul­ti-para­met­ric behav­ioral assays enabled far more accu­rate clas­si­fi­ca­tion of exper­i­men­tal groups com­pared to clas­si­cal tests, and dimen­sion­al­i­ty reduc­tion analy­sis demon­strat­ed sig­nif­i­cant addi­tion­al gains in clas­si­fi­ca­tion accu­ra­cy, high­light­ing the pres­ence of sex, envi­ron­men­tal and geno­type dif­fer­ences in our exper­i­men­tal groups. Togeth­er, our results pro­vide a com­plete phe­no­typ­ic descrip­tion of all test­ed groups, sug­gest­ing mul­ti-para­met­ric assays can cap­ture the entire spec­trum of the het­eroge­nous phe­no­type in autism mouse models. 

Biog­ra­phy

Alek­san­dra Badu­ra is an asso­ciate pro­fes­sor on Eras­mus Uni­ver­si­ty Med­ical Cen­ter (EMC) in Rot­ter­dam. She earned her Ph.D. in Neu­ro­science from Eras­mus Uni­ver­si­ty in Rot­ter­dam, where she stud­ied the effects of affer­ent inputs on cere­bel­lar activ­i­ty and motor coör­di­na­tion. In 2012 she has start­ed post-doc­tor­al fel­low­ship on Prince­ton University. 

There, using intrav­i­tal two-pho­ton imag­ing, she dis­cov­ered that gran­ule cells receive sig­nals pre­dict­ing motor per­for­mance, lead­ing to a shift in under­stand­ing cere­bel­lar cod­ing. She also devel­oped advanced tools for mon­i­tor­ing neu­ronal activ­i­ty via two-pho­ton imag­ing. In 2015 she moved to the Nether­lands Insti­tute for Neu­ro­science in Ams­ter­dam while con­tin­u­ing her role as a Vis­it­ing Research Col­lab­o­ra­tor at the Prince­ton Neu­ro­science Insti­tute. Her research focused on the cerebellum’s role in autism spec­trum dis­or­der (ASD).

She demon­strat­ed that cere­bel­lar deficits are com­mon in ASD and that dis­rup­tions to cere­bel­lar activ­i­ty dur­ing devel­op­ment cause abnor­mal cog­ni­tive and social behav­iors. In June 2018, she was award­ed a VIDI-Zon­Mw start­ing grant to inves­ti­gate the cere­bel­lo-cere­bral net­works under­ly­ing shared autis­tic traits (source: https://​pip​gen​.eu/​s​u​p​e​r​v​i​s​o​r​/​a​l​e​k​s​a​n​d​r​a​-​b​a​d​u​r​a​-​e​s​r7/). 

Web­page: https://​neu​ro​.nl/​p​e​r​s​o​n​/​A​l​e​k​s​a​n​d​r​a​-​B​a​d​ura