Development of a targeted drug delivery strategy to treat type 1 diabetes

Nikki Farnsworth

nfarnsworth@mines.edu

Project Background: The pancreatic islets of Langerhans regulate blood glucose homeostasis by secreting insulin. Type 1 diabetes is characterized by the immune-mediated destruction of insulin producing β-cells. The goal of this project is to investigate mechanisms of pancreatic beta-cell death in type 1 diabetes, with a focus on pro-inflammatory cytokine mediated cell death and to aid in the development of a targeted drug delivery strategy to protect against β-cell death. Specifically, this project will help to determine cell signaling pathways involved in regulating cell death in type 1 diabetes and will determine the pharmacological potency of a novel therapeutic target to prevent disease onset. This project is highly clinically relevant as the results from this study will help us to engineering better and more targeted therapies for patients with type 1 diabetes. This is multidisciplinary project that combines biomaterials, quantitative microscopy, cell biology, and biochemistry. Due to the translational nature of this project, the student will also have opportunities to interact with physicians and scientists on the Anschutz Medical Campus to further broaden their experience. In this project, the student will synthesize pcl nanocapsules varying protocol parameters (stir time/speed, etc.) and will quantify particle size and polydispersity. The student will also measure the release profile of fluorophore encapsulated in the nanocapsules over 1-2 weeks. The student will develop a protocol for immunoprecipitation of PKCδ and will use western blot to quantify post translational modifications to PKCδ, including phosphorylation and nitrosylation.   Objectives:

• Synthesize pcl nanocapsules using varied protocol parameters and quantify capsule formation success
• Measure drug and fluorophore release profile from nanocapsules
• Determine modifications to PKCδ using immunoprecipitation and western blot
• Develop protocol for immunoprecipitation

  Deliverables:

• Laboratory notebook with detailed experimental design and results
• PKCδ western blot data, drug release profile data, nanocapsule synthesis protocol immunoprecipitation protocol
• Final presentation describing the project significance, methods used, experimental results and analysis of the significance of the experimental findings

  Time Commitment: This Honors Undergraduate Research course is a 2 credit hour commitment, which translates to 8 hours per week. The Spring 2021 semester runs 17 weeks; therefore, a commitment of 136hrs for this semester is expected. The student is free to schedule this time as it fits with their course schedule. The final grade for this course is based on the total number of research hours completed.

Grand Challenge: Engineer better medicines.

Nikki Farnsworth, nfarnsworth@mines.edu | Jillian Collins, jcollins1@mines.edu