Dr. Paul Hamilton

Associate Professor
& Director, Master of Microbial Biotechnology (MMB) Program 

Microbial biotechnology, bacteriophage biology, biotechnology applications of thermophiles, phage display technology


Master of Microbial Biotechnology Program

The Professional Science Master’s degree in Microbial Biotechnology (MMB) at North Carolina State University provides students with training in cell and molecular technology and a working knowledge of the business components of the Biotechnology Industry.  The MMB program developed in response to the Biotechnology Industry’s desire for employees with a strong technical aptitude along with an understanding of business issues and well-developed professional skills. The MMB curriculum includes academic coursework in science and business along with professional training provided by local companies through case study projects and internships.  More information on the MMB program can be found at the MMB website.

Publications on the MMB Program 

Jason M. Cramer and Paul T. Hamilton (2017) An Internship May Not Be Enough: Enhancing Bioscience Industry Job Readiness through Practicum Experiences.  Journal of Microbiology and Biology Education, Volume 18, Issue 1

Sarah C. Luginbuhl and Paul T. Hamilton (2013) Cooperative Learning through Team-Based Projects in the Biotechnology Industry. Journal of Microbiology and Biology Education, Volume 14, Issue 2; p. 221-229

Paul T. Hamilton, Sarah C. Luginbuhl and Michael Hyman (2012) Preparing Science-Trained Professionals for the Biotechnology Industry: A 10-year Perspective on a Professional Science Master’s Program. Journal of Microbiology and Biology Education. Volume 13, number 1 pp.39-44.

 

Research Interests

As we enter a post-genomic era, it has become apparent that a significant number of the genes identified in bacterial genomes encode proteins of unknown function.  The development and refinement of tools and techniques to elucidate the function of these poorly characterized proteins will be required.  My research interests are in developing peptide-based tools to determine the role of various proteins of unknown function in bacterial metabolism and virulence.  In addition, many of the genes encoding proteins of unknown function are required for cell viability.  These essential genes represent valid targets for antibacterial drug discovery but are typically not accessible using standard biochemical assays.  The peptide-based tools developed to ascribe function to these essential gene products can be readily converted into high throughput screening (HTS) assays for drug discovery.

Determining the Activity for Bacterial Proteins of Unknown Function

Over 700 bacterial genomes have been completely sequenced and at least an equal number are in progress.  This work provides a large amount of genetic and genomic information; however, to extend the value of these data will require functional characterization of the gene products.  Mycoplasma genitalium has one of the smallest genomes of any free-living organism.  Characterization of the genes essential for M. genitalium viability has shown that 382 of the 482 M. genitalium protein-coding genes are essential. Of those 382 essential genes, 28% encode proteins of unknown function.  To take full advantage of the bacterial genomic information available and to have a more complete understanding of the role these proteins of unknown function in bacterial physiology will require additional tools.  High affinity binding reagents and inhibitors have traditionally been used as tools to characterize protein function.  Peptide-based phage display technology offers a way to rapidly isolate such reagents.

Phage display is a powerful technology that my lab has used to identify peptides that bind to a wide range of targets from proteins to biomaterials.  Combinatorial peptide libraries are constructed by inserting peptide-encoding oligonucleotides into gene III of bacteriophage M13.  The resulting peptide fusions are displayed on the surface of the bacteriophage and can be screened for binding to a target of interest.  When applied to protein targets, we have observed that the peptides are directed to functional sites on the protein and don’t bind randomly to the protein.  For an enzyme, this includes targeting the active site and the peptide will function as an inhibitor of the enzymatic activity, even if the enzymatic substrates are none peptidic in nature.  For example, we have isolated peptides that bind to alcohol dehydrogenase and inhibit the conversion of ethanol to acetaldehyde with a Ki of 80 nM.

In addition to their use as inhibitors in biochemical reactions, peptides can be expressed inside cells to bind the target protein and disrupt its function.  When applied to proteins that are essential for cell viability, this “protein knockout” will result in inhibition of cell growth.  We have validated this protein knockout approach with several essential bacterial proteins and want to apply it to proteins of unknown function that are indentified by genomics.

Antibacterial Drug Discovery

Infectious diseases are still a leading cause of death worldwide.  With increasing antibiotic resistance among bacterial pathogens and the emergence of hard-to-treat opportunistic infections, the need for new antibiotics continues.  Among pharmaceutical companies, however, antibacterial research and development has been downsized or eliminated.  Bacterial genomics has provided a large number of new targets for antibacterial drug discovery.  As described above, a significant number of the essential genes identified by genomics encode proteins of unknown function.  In previous work, we have shown that peptides isolated by phage display can be used as surrogate ligands to develop HTS-compatible assays to screen chemical compound collections for the discovery of new antibacterial agents.

My longer term goals include elucidating the role of proteins of unknown function in bacterial metabolism and virulence and developing small chemical molecules and peptides as research tools for characterization of bacterial proteins and enzymes.

Patents

  PAT. NO. Title
1 8,779,089 Methods and compositions for soft tissue repair
2 8,691,946 Methods and compositions for soft tissue repair
3 8,637,455 Compositions and methods for delivery of glycopeptide antibiotics to medical device surfaces
4 8,273,337 Hair binding peptides and peptide-based hair reagents for personal care
5 8,263,056 Dyed-hair-binding peptides and peptide-based hair reagents for personal care
6 8,067,021 Methods and compositions for delivery of growth factor to fibrous connective tissue
7 8,030,452 IFBM’S to promote the specific attachment of target analytes to the surface of orthopedic implants
8 8,022,185 IFBM’s to promote the specific attachment of target analytes to the surface of orthopedic implants
9 8,022,184 IFBM’s to promote the specific attachment of target analytes to the surface of orthopedic implants
10 8,022,183 IFBM’S to promote the specific attachment of target analytes to the surface of orthopedic implants
11 7,994,277 IFBM’s to promote the specific attachment of target analytes to the surface of orthopedic implants
12 7,972,615 Peptide compositions for coating metal medical devices with vancomycin
13 7,968,677 IFBM’s to promote the specific attachment of target analytes to the surface of orthopedic implants
14 7,812,119 IFBM’s to promote the specific attachment of target analytes to the surface of orthopedic implants
15 7,807,624 Methods and compositions for promoting attachment of cells of endothelial cell lineage to medical devices
16 7,795,383 IFBM’s to promote the specific attachment of target analytes to the surface of orthopedic implants
17 7,790,844 IFBM’s to promote the specific attachment of target analytes to the surface of orthopedic implants
18 7,786,256 IFBM’s to promote the specific attachment of target analytes to the surface of orthopedic implants
19 7,608,581 Biofunctional, antimicrobial coatings for medical devices
20 7,572,766 IFBMs to promote the specific attachment of target analytes to the surface of orthopedic implants
21 7,531,505 Compositions and methods for promoting attachment of cells of endothelial cell lineage to medical devices
22 5,888,795 Thermostable uracil DNA glycosylase and methods of use
23 5,736,373 Thermostable DNA polymerase from Bacillus pallidus
24 5,656,424 Identification of mycobacterium tuberculosis complex species
25 5,633,159 DNA polymerase III .beta.-subunit from mycobacteriophage DS6A
26 5,612,182 Mycobacteriophage specific for the mycobacterium tuberculosis complex
27 5,582,969 Mycobacteriophage specific for the mycobacterium tuberculosis complex
28 5,476,768 Mycobacteriophage DSGA specific for the mycobacterium tuberculosis complex