Cellular & Molecular Engineering Laboratory

David Raden

I am interested in integrating quantitative biological experimentation with engineering and mathematical methods to answer biological questions. I am involved in 3 ongoing projects...

Analyzing and Modeling the Early Secretory Pathway- A Systems Biology Approach to the Endoplasmic Reticulum

The Endoplasmic Reticulum (ER) is entry point to the secretory pathway. Secreted proteins, such as growth factors and growth factor receptors, that utilize the secretory pathway are first translocated into the ER or ER membrane. Once inside the ER, proteins interact with resident ER proteins that assist in their folding and modification. A signaling network is activated in response to the accumulation of unfolded protein that exceeds the folding capacity of the ER. The unfolded protein response of the ER (UPR) involves components and processes in the ER, cytoplasm, and nucleus.

The UPR in budding yeast has been well characterized in terms of factors in the pathway and assays for activation. Excellent work defining the UPR pathway provides an opportunity for further examination using kinetic analysis and modeling..
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The UPR in mammalian cells is more complex involving at least three signaling cascades with some degree of crosstalk. The UPR has been implicated in a number of diseases including neurodegenerative diseases and diabetes. The UPR activates components for adaptation to the stress and cell death. A model of these competing pathways can lead to a better understanding of cell fate.

Stochastic Modeling of Protein Interactions in the ER

This research focuses on the effects of the suborganellular distribution of proteins on regulation of cellular functions. The complex heterogeneous environment of the cell, where protein concentrations will vary from their overall cellular concentration, has not been adequately quantitated. In this work protein distribution is being examined by developing a mathematical framework for heterologous protein distribution and integrating it with rigorous mathematical modeling and a quantitative experimental approach in two biological processes.
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Optimization of Molecular Biology Techniques by Design of Experiments Methodologies

Design of Experiments (DOE) applies a systematic approach to the understanding and optimization of components of a system or process. Applying DOE to biological systems allows us to determine the important components (reagents, time, process) and test for interactions between these components within a resonable number of experiments.

Contact Information:
David Raden
365 Colburn Laboratory
Department of Chemical Engineering
University of Delware
Newark, DE 19716

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