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Synthetic gene circuits for regenerative engineering

Primary Investigators:
Jonathan Brunger
 
Brief Description of Project:
Our lab takes a multi-disciplinary approach that integrates tissue engineering, synthetic biology, pluripotent stem cell technology, and genome engineering to understand diseases and design cell-based therapeutics. We have recently developed new methods to enable cells to sense features of a niche that are consistent with musculoskeletal pathology and neurodegeneration. We have shown we can then program these cells to execute defined scripts to locally activate cell differentiation, production of therapeutic compounds, or expression of genes that may help us dissect molecular bases for disease.

This project will involve contributions in the following areas of these investigations:

  • Design and assembly of new gene circuits to control cell behaviors relevant to musculoskeletal regenerative medicine and studies of neurodegeneration
  • Production of gene delivery vehicles for implementation of cell engineering strategies
  • Cell-based and molecular assays (e.g., flow cytometry, luminescence assays, immunocytochemistry, ELISAs, gene expression profiling) to determine specificity of circuit responses and impact on cell and tissue function

Desired Qualifications:
Highly motivated students interested in research who have taken general chemistry and biology.
 
Nature of Supervision:
Hands-on training and support will be provided by a graduate student, who will serve as the researcher's primary mentor and interact directly on a daily basis. The student will participate in weekly lab group meetings. The undergraduate researcher will meet with the PI at least bi-weekly to discuss research progress.
 
A Brief Research Plan (period is for 10 weeks):
After completing safety training and acclimating to the lab during week 1, the student will be involved in cloning, sequencing, and purifying new gene expression vectors (wks 2-3). Lentivirus will be produced and used to engineer target cells (e.g. pluripotent stem cells, immortalized cell lines) with gene circuit platform components (wks 4-5). Students will then assess the influence of the artificial signaling circuit by a variety of outputs that may include measurement of reporter transgene expression (e.g., fluorescence microscopy, flow cytometry, luminescence assays), immunolabeling, qRT-PCR, and RNAseq (wks 6-9). The student will then prepare a final report and poster presentation during week 10.
 
Number of Open Slots: 2
 
Contact Information:
Name: Jonathan Brunger
Department: Biomedical Engineering
Email: jonathan.m.brunger@vanderbilt.edu