Transcript PP Presentation

Phage Nanobiotechnology
Tatiana Samoylova
Phages – ideal naturally occurring
nanomaterials
• phages - viruses that infect bacteria
• exhibit a great diversity of shapes in nanometer
range (examples below)
• well-defined geometry and uniformity favorable
for nanofabrication
• phage coat proteins can be engineered using
simple recombinant DNA techniques
Segment of ~1% of filamentous landscape
phage particle. Phage coat proteins are
grey. Engineered fusion peptides are black.
V. Petrenko.
Phage Lambda,
http://textbookofbacteriology.net/phage_2.
html
Filamentous M13 phage, EM image.
T. Samoylova
Phage Nanobiotechnology
Tatiana Samoylova
Phage display technology
• set of phage-based techniques for identification of target-specific
peptides or proteins
• targets include biomolecules, whole cells, whole tissues in living
organisms, non-biological surfaces (for example, metals)
• phage display libraries are mixtures of distinct phage clones
• filamentous phage is predominant phage display vector
• library consists of billions of phage clones – billions opportunities to
select phage clones specific to desired targets
900 nm
7 nm
pIII
pVI
pVIII
pVII + pIX
Phage Nanobiotechnology
Tatiana Samoylova
Phage display technology
• set of phage-based techniques for identification of target-specific
peptides or proteins
• targets include biomolecules, whole cells, whole tissues in living
organisms, non-biological surfaces (for example, metals)
• phage display libraries are mixtures of distinct phage clones
• filamentous phage is predominant phage display vector
• library consists of billions of phage clones – billions opportunities to
select phage clones specific to desired targets
900 nm
g8
pIII
pVI
7 nm
pVIII
pVII + pIX
Phage Nanobiotechnology
Tatiana Samoylova
What we are doing with phage nanomaterials
(current focus)
• whole phage particles as vaccines for contraception of animals (cat/dog/pig)
• phage particles that display peptides with contraceptive properties
- GnRH peptide, zona-pellucida binding peptides
- phage body – carrier protein, peptides – antigens
• phage is effective immunogen (nanosize, architecture), low cost, stable, safe
• shown below – sperm-oocyte interaction in in vitro fertilization experiment in the
presence of (A) normal serum or (B) serum from immunized animal
B
A
Normal porcine serum
Porcine anti-serum, contains antisperm antibodies
Phage Nanobiotechnology
Tatiana Samoylova
What others at AU are doing with phage
nanomaterials
• targeted liposomes with phage fusion proteins for cancer-specific
drug/gene delivery (V Petrenko, CVM, illustration below)
• devices for pathogen detection using filamentous phage
(Bryan Chin, AU Detection and Food Safety Center)
• devices for detection of bacterial infection using lytic phage
(Aleksandr Simonian, College of Engineering)
• fabrication of phage-based biosensors (V Vodyanoy, CVM)
• magnetic nanoparticles targeted with phage-derived
peptides for imaging of brain tumors
(A David, College of Engineering, illustration on the right)
Multi-domain cores
+
100 nm
Magnetic nanoparticles targeted to brain
tumor with phage-derived peptides
Landscape phage coat
protein units displaying
tumor- specific peptide
Therapeutic liposome
containing drugs
Tumor-targeted liposome
Phage Nanobiotechnology
Phage nanomaterials in medicine
and technology: applications
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affinity matrix for purification of biomolecules
scaffold for tissue engineering/repair
medical diagnostics and monitoring
molecular imaging
targeted drug and gene delivery
vaccine development
detection of pathogens and biothreats
in microelectronics, as template for fabrication of
nanowires and nanocomposite films
• details in this book
New hires for AU
• bioinformatics
• computational proteomics
• systems biology (systeomics)
Tatiana Samoylova