The Center for Experiential Learning and Diversity

Chemical Engineering Lab

PI: Dr. Elizabeth Nance, eanance@uw.edu

Immediate Mentor/Supervisor: Chad Curtis, ccurtis7@uw.edu; Mike McKenna, mimc7580@uw.edu

Start-Up Company Name: TBD

Lab/Project Website: nancelab.com

Work Location: Benson Hall 215

Work Hours: 9 am – 5 pm, Monday – Friday. Some weekend days may be necessary, but will be coordinated well in advance and would replace a work weekday. Lab meetings are weekly and 1.5 h in length. Lab meetings are scheduled on a quarterly basis, and take place in the 9 am – 5 pm, Monday – Friday window, at the same time/day every week.

Overall Program Goal: Effective treatment of central nervous system diseases is a major challenge due to the inability of many therapeutics to cross the blood-brain barrier and penetrate within the brain extracellular space (ECS). In developing a high-throughput platform to assay nanoparticle behavior in the brain microenvironment, there are four components we aim to develop: (1) a viable organotypic slice platform that can adapt to multiple species and disease models, (2) well-characterized probe nanoparticles with a variety of physicochemical properties, (3) a high spatial resolution setup for real-time and time-lapse imaging of nanoparticles and cells, and (4) a Python code and computational software package to extract information from the imaging setup to generate useful, robust outcome data. We are pursuing micro and macroscopic characterization of colloidal and transport behavior in the brain as a function of physiological factors, age, brain region, disease, nutrition, and design of the probe particles. We currently are interested in developing complimentary models to this slice platform, including agarose gel models, primary cell and cell culture models. In our agarose gel models, we are interested in building a 3D system that represents the complexity of the brain microenvironment. Our preliminary work has focused on embedded extracellular matrix proteins into agarose gels or embedding pluronic tubes in agarose gels to model blood vessels. Our next steps are to combine the blood vessel agarose gel model with the extracellular matrix protein gel model, and evaluate bulk rheology, bulk viscosity and microviscosity. To do this, we need to adapt our imaging analysis to time-lapse imaging of probe nanoparticle movement from blood vessels into the gel (i.e the extracellular space).

Intern Project Description and Responsibilities: The intern will be responsible for embedding pluronic tubes into protein loaded agarose gels. The intern will then perfuse the tubes with probe nanoparticles and time-lapse image the permeation of those nanoparticles from the tube into the agarose gel. If the student progresses well with this experimental setup, the student will get an introduction to particle tracking to track the individual nanoparticle trajectories generated from the time-lapse videos. The intern on this project will learn the following techniques: formulation of agarose gels, characterization of gels using a parallel plate rheometer, formulation of probe nanoparticles and size and surface charge characterization of probe nanoparticles using dynamic light scattering, an introduction to confocal imaging, and an introduction to ImageJ and Python.

Pre-requisites: The student should be enthusiastic about the work, and interested in learning both engineering, biophysics, and some biological techniques. The student does not need prior background in nanotechnology, biology, or neuro. If the student comes in with a passion and interest in learning, getting their hands dirty, and working within a highly collaborative team environment with some risk, but a lot of reward, then they will be a good fit for our group! We would prefer a student who’s time in our lab would benefit their career development and align with their career goals (i.e. interest in an MD, PhD, or MS degree, interest in R&D in the biotech industry).

Level of Independence: The lab is well-structured for mentoring, and the student has the flexibility to decide how to utilize that structure to meet their needs. There are two graduate student mentors who will be involved in the development of this project, and have different, but very supportive mentoring styles. The student is expected to have high motivation and a strong work ethic. A willingness to work in a team, but be a key player that is relied on by the team, is important. Past summer students have put in a minimum of 40 hours a week because of their investment and interest in the lab projects.

The student will be part of a subgroup led by Chad and Mike. This subgroup meets each week informally to discuss weekly results, and brainstorm ideas or troubleshoot ongoing experiments. Additionally, the student will be expected to present both a journal critique and a project presentation in lab meeting once during the summer.

Learning Opportunities:

  • Learn the importance of ex vivo and in vitro models and how they complement in vivo studies for brain-related applications.
  • Be able to identify the challenges of treating brain diseases and the limitations in designing therapeutics for the brain.
  • Develop an appreciation for how understanding basic principles like diffusion can direct our engineering of therapeutic platforms
  • Demonstrate the ability to communicate (written, oral, and visual) to a diverse audience

Additional info: The lab has a strong track record of mentoring students for summer projects. We have had 4 high school students successfully complete and present 6-10 week projects. We currently have 11 undergraduates in the group, from a diverse set of majors, including chemical engineering, bioengineering, public health, molecular/cell/developmental biology, and preengineering. We are always excited to have new people join our lab and become a part of the Nance lab culture!