Biosystems Dynamics Summer Institute at Lehigh University

 

Research Projects - 2017

Click on the team name tab to read about their research.

Brown | Pires Team

Project Title:

Characterization of bacterial outer membrane vesicle-associated peptidoglycan via unnatural D-amino Acids

Project Description:

Bacteria continue to pose a tremendous threat to public health because of the increase in drug-resistance. Recently, it was discovered that bacterial cells will release tiny vesicles (pieces of themselves) starting at the point it firsts infects a patient and throughout the infection period. While the details are yet to be fully worked out, it is well-established that these vesicles play a very important role in defining the course of infection. The Brown and Pires laboratories are interested in studying how these vesicles can carry fragments of cell walls that are detected by the human immune system. To accomplish this, they will combine their expertise in manipulating them to tag the fragments of cell walls and visualize its interaction with human immune cells. They aim to use these observations to define the steps in vesicle binding to immune cells and the ultimate mediators of immune cell activation.

 

Team Leaders:

Angela Brown, Ph.D. - Chemical Engineering
Marcos Pires, Ph.D. - Chemistry

 

Chow | Jedlica Team

Project Title:

Self-assembling hydrogels based on glycosaminoglycan-peptide hybrid molecules

Project Description:

Biomaterials can be designed to mimic the extracellular matrix (ECM) that surrounds cells to improve tissue regeneration in the body. The ECM is composed of many different biomolecules with concentrations that vary depending on the tissue or organ type. In addition, the ECM is a dynamic environment that is constantly changing under normal conditions and due to injury or disease. Glycosaminoglycans (GAGs) are one important class of ECM molecules that play a major role in numerous biological processes. We recently developed strategies to modify GAGs with self-assembling peptides to create a dynamic GAG-peptide hydrogels. This BDSI project will focus on characterizing hydrogel properties and investigating how cells behave inside the hydrogel. The interdisciplinary team will work on three key objectives: (1) synthesizing self-assembling GAG-peptide hybrid molecules; (2) characterizing the properties of the GAG-peptide hydrogels; and (3) investigating how hydrogel composition and properties affect human mesenchymal stem cell (hMSC) behavior. Students will learn a wide range of techniques across disciplines such as chemistry, materials science and engineering, bioengineering, and biological sciences. The results from this BDSI project will help guide the design of future ECM-like hydrogels to drive desired cell behavior. 

Team Leaders:

Lesley Chow, Ph.D. - Materials Science and Engineering
Sabrina Jedlicka, Ph.D. - Materials Science and Engineering

 

Dailey | Zhang Team

Project Title:

AFM Naniondentation Goes Deeper – Experimental and Computational Investigation of Substrate Stiffness Effects on Apparent Cell Elasticity

Project Description:

Atomic force microscopy (AFM) is an experimental technique for measuring the mechanical properties of biological cells. In an AFM experiment, a very small bead is attached to the end of a micro-cantilever and pressed into the surface of a cell with a force of several hundred piconewtons (one piconewton = one trillionth of a newton, where a newton is the average weight of an apple). A laser system tracks how deeply the bead indents into the cell and a computer program is used to process the recorded data and estimate the mechanical stiffness or elasticity of the cell. Many factors can influence how soft or stiff a cell appears to be, including the shape and size of the cell itself and the size of the bead that is used to indent the cell. We also hypothesize that the elasticity of the substrate, or surface on which the cell grows, can also change how soft or stiff the cell appears to be when probed by AFM nanoindentation. In this summer project, students will grow cells on substrates of different stiffness and use an AFM system to measure cell elasticity. Students will also use a computer simulation technique called finite-element analysis (FEA) to model bead indentation into cells. We will compare the measurements from the AFM experiments and the predictions from the computational models to study the how the substrate influences whether the cell appears to be soft or stiff due to its environment.

Team Leaders:

Hannah Dailey, Ph.D. - Mechanical Engineering and Mechanics
Frank Zhang, Ph.D. - Mechanical Engineering and Mechanics

Im | Honerkamp Smith | Wittenberg Team

Project Title:

Distributions and Orientations of Gangliosides in Membranes

Project Description:

We have formed an interdisciplinary group to study a class of molecules which are called gangliosides because they are found on the surface of brain cells. They form part of the lipid membrane, which is the barrier between the cell’s inside and outside. One group of experimentalists will measure how these molecules influence the rupturing of lipid membranes.  Another group will use microscopy to observe how gangliosides move when flow is applied to the membrane. While these experiments are going on, theorists will conduct simulations to see the molecular-scale details of ganglioside interactions. 

Team Leaders:

Wonpil Im, Ph.D. - Biological Sciences
Aurelia Honerkamp Smith, Ph.D. - Physics
Nathan Wittenberg, Ph.D. - Chemistry

 

Miwa | Im | Zhang Team

Project Title:

Probing receptor binding capabilities of mutant lynx modulators for better cognition and emotional processing

Project Description:

Anxiety disorders are among the most common mental disorders in the US but current methods to treat anxiety provide temporary relief and do not address the root cause.  We find that a protein LYNX plays a role in modulation of anxiety and is a good candidate as a novel target to alleviate anxiety. Several natural genetic variations to the lynx protein in humans, introduced by natural mutations in the gene, single nucleotides polymorphisms (SNPs), have been characterized. We predict that these mutations affect protein function, and thus an individual’s response to anxiety. 

We want to test this hypothesis by assaying the relevant mutations functionally. We aim to produce the normal SNP variants of the protein, and test their binding characteristics using atomic force microscopy (AFM) in cells expressing their cognate receptor, nicotinic receptors. We will also model computationally lynx/receptor interactions to understand the critical amino acids and the effect of SNP mutations on binding.

This project is interdisciplinary involving protein biochemistry, neuroscience, atomic force microscopy, computational modeling, and could also lead to more functional studies with electrophysiological and behavioral assays. These studies could provide a critical causal link between lynx and anxiety regulation, which could have a beneficial impact on human health and well-being.

Team Leaders:

Julie Miwa, Ph.D. - Biological Sciences
Wonpil Im, Ph.D. - Biological Sciences
Frank Zhang, Ph.D. - Mechanical Engineering and Mechanics

 

 

 

 

 

 

 

 

Biosystems Dynamics Summer Institute at Lehigh University
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