Current Projects

 

Targeting Bacteriophage Delivery to Astrocytes

The filamentous bacteriophage M13 is a single-stranded DNA phage that co-exists with its Escherichia coli host after infection. M13 possesses several attractive characteristics for gene delivery and have a well-documented ability to cross the blood-brain barrier which is an exploitable trait that can be applied to targeted phage delivery to the CNS. Astrocytes have been shown to differentiate into functional neurons. This ability makes them an ideal target for gene delivery and cell transformation.

The goal of this project is to show that intravenous administration of M13 miniphagemids, engineered to carry LCC DNA vectors (iPhAGEs) will effectively cross the blood brain barrier and allow for the reprogramming of astrocytes.

Novel Biomanufacturing of Adeno-Associated Virus Platform

Adeno-associated virus (AAV) is an unenveloped virus classified in the Parvoviridae family, known for its ability to effectively and securely transport genetic material into cells, making it valuable for gene therapy. Although industrial manufacturing methods for AAV vector production have advanced, challenges remain in terms of quality and production costs, hindering wider development. The limited scalability of current methods has resulted in prohibitively high costs for many patients seeking AAV gene therapy.

iPhAGES Platform Optimization and Applications

Molecular targeted therapy has emerged as a promising strategy to treat cancer over the last several years. Unlike the broad-spectrum cytotoxic drugs prescribed for conventional chemotherapy, targeted therapy is designed to address specific molecular changes which are unique to a specific cancer type. To develop a successful targeted therapy, many delivery platforms have been investigated to optimize safety, specificity and efficiency.

 

Identification of E. coli Host Genes Influencing T4rII Exclusion Phenotype

The rex genes (rexA, rexB) of bacteriophage Lambda (λ) are able to prevent mutant bacteriophage T4rII plaque formation on E. coli hosts lysogenized by λ. The expression of these two genes of the Rex system is primarily regulated by the repressor gene cI from the PM promoter.

This project aims to isolate and identify relevant host mutations that could influence the Rex phenotype. Through this work, the manifestation of Rex has been linked to genes underlying key host stress responses.

The Effects of Amyloid-Beta on Neuronal Transcription

Alzheimer’s disease (AD) is a prevalent neurodegenerative disorder, associated with a decline in cognition and impaired episodic memory. This disorder is well known for its behavioural phenotype, however knowing its cellular pathology, which is primarily based on the presence of Amyloid β (Aβ) in various aggregation states, is crucial for the development of research efforts against the disease.  

As such, this project aims to determine what the downstream effects of Aβ are on neurons and by doing so illustrate what deleterious effects Aβ causes. To accomplish this goal the transcriptomic profile of neuronal cells exposed to these aggregation states of Aβ was quantified.

 

A selection of associated publications:


Research Articles

  1. Construction and characterization of a novel miniaturized filamentous phagemid for targeted mammalian gene transfer. Read here.

  2. The effects of amyloid beta aggregation on neuronal transcription. Read here.

  3. EGFR-targeted bacteriophage lambda penetrates model stromal and colorectal carcinoma tissues, is taken up into carcinoma cells, and interferes with 3-dimensional tumor formation. Read here.

  4. A snapshot of the λ T4rII exclusion (Rex) phenotype in Escherichia coli. Read here.

  5. Identification of Escherichia coli Host Genes That Influence the Bacteriophage Lambda (λ) T4rII Exclusion (Rex) Phenotype. Read here.

  6. Lambda bacteriophage nanoparticles displaying GP2, a HER2/neu derived peptide, induce prophylactic and therapeutic activities against TUBO tumor model in mice. Read here.

  7. Immunogenicity and antitumor activity of the superlytic λF7 phage nanoparticles displaying a HER2/neu-derived peptide AE37 in a tumor model of BALB/c mice. Read here.

  8. Lambda Phage nanoparticles displaying HER2 derived E75 peptide induce effective E75-CD8+ T response. Read here.

  9. Construction and analysis of a genetically tuneable lytic phage display system. Read here.

  10. Graphical analysis of flowcytometer data for characterizing controlled fluorescent protein display on Lamba phage. Read here.

Review Articles

  1. Advances in gene-based vaccine platforms to address the COVID-19 pandemic. Read here.

  2. Bacteriophage interactions with mammalian tissue: Therapeutic applications. Read here.

  3. The viral approach to breast cancer immunotherapy. Read here.

  4. Phage-based nanomedicines as new immune therapeutic agents for breast cancer. Read here.

  5. Bacteriophage lambda display systems: developments and applications. Read here.


Patents

  1. Vectors for Producing Virus-Like Particles and Uses Thereof. Find online.

  2. DNA Vector Production System. Find online.

  3. DNA Vector Production System. Find online.

  4. EGFR Binding Moiety-Presenting Bacteriophages for Tumor Treatment. Find online.

  5. Fusion Protein Comprising Bacteriophage  λ GPD  Fused to a GP2 Antigen Derived from HER-2/NEU. Find online.

  6. Peptide Displaying Bacteriophage Nanoparticles and Related Compositions and Methods. WO 2019/102265 A1. Find online.


Books

  1. Gene Delivery Imaging and Evaluation Systems. Find online.

  2. Bacteriophage Applications - Historical Perspective and Future Potential. Find online.