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Lab for protein & immuno-engineering!!Professor Jennifer Maynard, !Chemical Engineering, UT Austin!

Biologics  drive  biotech  &  pharma  industries  

15.6   16.9   18.5   20.3   24.6  

0  

10  

20  

30  

40  

50  

60  

2008   2009   2010   2011   2012  

US  Biotech  Sales,  $  Billions  

An/coagulants  

Recombinant  Vaccines  

Enzymes  

Blood  Factors  

Cytokines  

Fusion  Proteins  

Hormones  

Growth  Factors  

46.7   48.3  51.6   52.5  

63.6  

§  An/body  drugs  generate  >  $25  Billion  in  US  sales1  •  38  approved  mAbs,  8  under  review2  

1.  Aggarwal,  S.  (2014).  Nature  Biotechnology  

2.  Reichert,  J.  (2014).  www.an/bodysociety.org/news/approved_mabs.php  

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Bacterial  infec7ous  diseases  

X  X  

Bacteria  Toxin  

Immune  responses  

T  cell  receptors  

   TCR  

An/bodies  

Innate    immunity  

Antibody-antigen interactions

Cell!Toxin!

neutralizing!antibody!

non-neutralizing!antibody!

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   1.  An7bodies  to  pertussis  toxin  

1B7  

11E6  

Goal  –    An/body  therapy  to  prevent  &  treat  pertussis  

   1.  An7bodies  to  pertussis  toxin  Goal  –    An/body  therapy  to  prevent  &  treat  pertussis  

Reducing Non-reducing

m11E6

ch

11E6

h11E

6

50 kD

25 kD

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2.  An7gen  engineering  for  pertussis    vaccines  (ACT)  

ATP  cAMP  

CaM  

Cataly/c  Domain   Hydrophobic  Domain  

Repeat  Region  (RTX)   Secre/on    Signal  

0     400   500   700   1000   1600   1706  AA  

98%  an/bodies,  Block  receptor  binding  

2%  an/bodies   Immunize  with  ACT  

Immunize  with  RTX  Induce  similar    An/bodies,  protec/on  

Goal  –    Design  an/gen  variants  with  enhanced  expression  levels  &,  stabili/es  that  induce  high  levels  of  protec/ve  an/bodies  

2.  An7gen  engineering  for  pertussis    vaccines    

Cataly/c  Domain   Hydrophobic  Domain  

Repeat  Region  (RTX)   Secre/on    Signal  

0     400   500   700   1000   1600   1706  AA  

ATP  cAMP  

CaM  

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3.  T  cell  receptor  (TCR)  responses:  CMV  

Goal  –    Understand  role  of  TCR  affinity  in  disease  and  protec/on      (UT  collaborator:  Lauren  Ehrlich,  Molecular  Biosci)  

 

APC  

1-­‐11  MBP  pep/de      I-­‐Au  MHC  

   172.10  TCR  

Human  cell  

peptide! MHC!

T  cell  

TCR!

Human  cell  

peptide! MHC!

soluble, high affinity TCR!

Engineer  binding  rates  from  ~5  uM  Kd  to  low  nM  to  high  uM  

Measure  2D  affinity;  Ac/va/on  on  cells  

In  vivo  retrogenic  mice:  What  affinity  TCR  persist;  what  cell  types;  what  affinity  clones  control/  induce  disease    

T  cell  

TCR*!

Power  of  engineering  Understand  underlying  biology  such  that  we  can  develop    design  rules  to  predictably  manipulate  systems  

Basic  science                      Applied  science  

Skills  in  protein  engineering  using  the  following  techniques:    Recombinant  Techniques    Protein  Expression  in  Eukaryotes,  insect  cells  and  Bacteria  (E.  Coli)    Protein  CharacterizaIon    Protein  CrystallizaIon    Cell  Culture  

Job  opportuni7es:  academics,  biotechnology,  pharmaceutrical  industries  

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The  Maynard  laboratory  is  offering  1  graduate  research  assistant    posi/on  in  in  the  areas  of  vaccine  design    Contact:  maynard@che.utexas.edu      Members  of  the  lab  (not  pictured:  Sr.  Scien/st  Dr.  Annalee  Nguyen)  Row  1:  Liz  Bogardus,  Ellisa  Leonard,  Jeong-­‐min  Hyun,  Edith  Acquaye,  Ellen  Wagner.  Row  2:    Josh  Laber,  Chris  Stevens,  Zach  Frye,  Kevin  Entzminger,  Xian-­‐zhe  Wang.