Trn proteins into strctre t n help iscover new therpetics.
bot Lesh Biosciences
t Lesh Bio, we re nleshing the power of mchine lerning to solve meicinl chemistry n crete new therpies for evstting iseses. escription
eprtment: Smll Molecle rg iscovery (SM)
Reports to: Senior irector, Smll Molecle rg iscovery
Level: Scientist or Senior Scientist (commensrte with experience)
The Position
The molecles we fin vi EL screening re only s goo s the trgets we pt in front of them. In SM, strctre-enble rg iscovery strts with protein - n it strts with yo. We re looking for hns-on protein biochemist to own the lrge-scle proction n chrcteriztion of high-qlity, intrcelllr protein trgets tht fel or hit-fining, biophysics, n strctrl biology efforts.
Yo will generte milligrm qntities of chllenging intrcelllr proteins n mlti-sbnit complexes from mmmlin n bclovirs expression systems, prify them to the homogeneity tht ownstrem science emns, n rigorosly chrcterize them so tht every regent leving yor bench is fit for prpose. Yor protein will irectly enble EL screens, SPR cmpigns, SR cycles, crystllogrphy, n cryo-EM - the experiments tht trn trgets into strctres n strctres into meicines.
This is bench-forwr role for scientist who tkes prie in regent qlity, thrives on ifficlt trgets, n wnts their work to be the fontion tht n entire iscovery progrm is bilt on.
In this role, yo will:
esign n execte prifiction strtegies for intrcelllr proteins, omins, n mlti-sbnit complexes expresse in mmmlin (Expi293 / BcMm) n bclovirs-insect (Tni) systems, t scles from screening (sb-liter) to strctrl n biophysics cmpigns (mlti-liter).
Operte n evelop methos on ÄKT FPLC pltforms cross ffinity, ion exchnge, hyrophobic interction, n size-exclsion chromtogrphy to eliver protein of efine prity, stoichiometry, n stbility.
Chrcterize ientity, prity, oligomeric stte, n homogeneity sing SEC-MLS s primry reot, complemente by SS-PGE, nlyticl SEC, n orthogonl biophysicl methos.
Proce SPR-gre n strctre-gre mteril, prtnering closely with biophysics n strctrl biology colleges to ensre regents meet the emns of bining sties, crystllogrphy, n cryo-EM.
Trobleshoot expression n prifiction of ifficlt constrcts - low-yiel, ggregtion-prone, chperone-epenent, or compositionlly complex ssemblies - n iterte on constrct esign n conitions to improve behvior.
evelop, ocment, n trnsfer robst, reprocible protocols; mintin rigoros recors n contribte to cltre of t qlity n regent trcebility.
Commnicte reslts clerly to cross-fnctionl iscovery tem n help prioritize pipeline of trgets ginst project timelines.
Who Yo re
Ph.. in biochemistry, strctrl biology, moleclr biology, or relte fiel, with 3-5 yers of relevnt instry experience spporting protein prifiction n chrcteriztion. (Eqivlent experience t the M.S. level with strong instry trck recor will be consiere for the Scientist level.)
emonstrte, hns-on expertise prifying intrcelllr proteins from mmmlin n bclovirs/insect cell systems t preprtive scle. ntiboy experience will not be consiere relevnt for this position.
eep, inepenent proficiency on ÄKT FPLC systems n strong commn of mlti-step chromtogrphic prifiction strtegy.
Prcticl experience with SEC-MLS (e.g., miniWN-clss etectors) for molr mss n oligomeric-stte etermintion, n n nerstning of its ssmptions n limittions.
Fmilirity with common ffinity-tg strtegies (e.g., His, Twin-Strep, Protein Select / StrepTctin n IMC-bse cptre) n son jgment bot tg selection n its impct on foling, solbility, n yiel.
trck recor of elivering protein regents tht enble ownstrem SPR n strctrl biology (crystllogrphy n/or cryo-EM).
Strong orgniztionl, ocmenttion, n commniction skills, n the bility to mnge mltiple trgets in prllel ginst project priorities.
Preferre Qlifictions
Experience prifying mlti-sbnit complexes n reconstitting efine-stoichiometry ssemblies.
Fmilirity with mlti-gene/mlti-cssette expression toolkits (e.g., MltiBc / biGBc, BcMm) n bclovirs genertion, mplifiction, n titering.
Hns-on biophysicl n nlyticl chrcteriztion beyon SEC-MLS - mss photometry, ntive MS, LS, nnoSF/therml shift, or intct-mss LC-MS.
irect experience generting crystllogrphy- or cryo-EM-gre smples, incling bffer optimiztion n stbility screening.
Experience spporting smll-molecle iscovery (EL, HTS, frgment, or strctre-bse cmpigns) n working longsie meicinl chemistry, biophysics, n compttionl colleges.
Comfortble with constrct esign t CROs n hnling commniction.
The Next Step is Yors
If yo wnt yor science to be the berock of EL-enble iscovery engine - n yo tke rel stisfction in hning college tbe of protein tht jst works - we' like to her from yo. Bring yor rigor, yor problem-solving, n yor love of ifficlt trgets, n help s trn proteins into strctres n strctres into meicines.
Who We re
Lesh Bio is Slt Lke City-bse biotechnology compny nleshing mchine lerning to solve meicinl chemistry problems. We believe the brekthrogh in preicting which smll molecles bin which proteins won't come from better lgorithms lone - it will come from better t, generte t scle the fiel hs never h. So we bilt the engine to proce it: we esign or own protein constrcts, generte the bclovirses tht encoe them, express them in insect cells, prify them with lb tomtion, n screen them ginst millions of N-encoe compons - mesring smll molecle-protein interctions by the billion. Tht t trins moels bilt to esign novel therpetics for trgets tht hve long resiste smll-molecle pproches. The proteins proce in this role re the literl sbstrte of tht mission: no protein, no mesrement; no mesrement, no moel. If yo wnt yor work t the bench to compon into something fr lrger thn ny single progrm, this is the plce to o it.
Benefits incle helthcre, 41K mtch, stock options, free lnches, n ccess to some of the best otoor loctions in the contry.
Slry
$1, - $16, per yer
