Summary of Research
in the Klauda Lab
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Alzheimer's Disease
Alzheimer's Disease (AD) is an increasly important neurodegenerative disease that is effecting the aging population with limited drug options for treatment. We are collaborating with Dr. Antonio Cardone (NIST) on probing an important mechanism associated with AD. Cdk5's hyper activation is known to result in pathologies that lead to AD. This occurrs when Cdk5 is activated by another protein. Our work aims to deactivate this complex which will prevent AD pathologies.
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Enzyme Design and Health
We are currently working on methods to design enzymes that are multifunctional against varied polysaccharides. Molecular simulations and wet lab assays are used train machine learning algorithms to provide predictions on how to improve enzyme activity. Moroever, we have specific interest in the Smlt1473 enzyme that is connected to opportunistic infections seen in cystic fibrosis patients.
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COVID-19 Research
Due to the COVID-19 pandemic in 2020, our lab has been involved with research to aid in understanding the mechanism of virus attachment to the host and proteins associated with virus virulence. This work is all done in collaboration with Dr. Bryan Berger's lab at UVA.
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Cell Membrane Modeling
One emphasis on research in the lab is modeling cellular membranes. We have modelled membranes from bacteria and yeast and their organelles. We are currently interested in outer membranes of gram negative bacteria and how these can result in autoimmune diseases attacking the nerve membranes. Membrane models of human cell membranes, e.g. the mylenin sheath, skin, and ocular lens, are also of current interest.
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Force Field Development
To accurately model cell membranes, the mathematical function used to describe molecule-molecule interaction must be accurate. Our lab is a leader in the field to develop an accurate and diverse force field for lipids (CHARMM36 and CHARMM36UA). We continue to add to diversity of this force field and fix current deficiencies. We are also involved in the next generation force fields that include polarization (Drude) in collaboration with Alex MacKerell (UMB), Richard Pastor (NIH), and Benoit Roux (U. Chicago).
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Peripheral Membrane Proteins (PMPs)
PMPs are proteins that bind to the surface of the cell membrane to perform their funciton. We currently study a protein involved in lipid exchange between cellular organelles, known as the Osh4 protein of yeast. This protein has been shown to form membrane contact sites (MCS) and this function is believed to facilitate lipid exchange. Our simulations are probing the mechanism for lipid and cholesterol exchange within the cell.
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Transmembrane proteins
Transmembrane proteins are proteins that span the cell membrane. Some of these are important proteins that transport molecules, such as drugs, across the rather impermeable membrane. We currently study various secondary active transporters that are involved in drug transport. We also have interest in proteins that are involved in recognizing serotonin at the neuron synapse and large signaling proteins involved in growth (plexins).
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Traditional Chemical Engineering
We also do reserach outside the biological area applied to traditional areas of chemical engineering, e.g., asphaletene aggregration, gas hydrates, and self-assembly formatoin. Our current interests in gas hydrates is understanding the molecule-scale growth of hydrates for use in separating and purifying gasses. We also are interested in quantifying the ability to use gas hydrates to squester carbon dioxide.