Meet Michael Kent
Michael S. Kent, Ph.D.
Member of the Technical Staff at Sandia National Laboratories from 1992 - 2024 (recently retired)
(Note – this website is my personal endeavor and is completely independent of, and not endorsed by, Sandia National Laboratories.)
Appointments:
1990 - 1992 Postdoctoral fellow, University of Paris VI and the Curie Institute, Paris, France
2006 - 2021 Staff Scientist at the Joint Bioenergy Institute (JBEI), Emeryville, CA
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2024 - present Fellow, Discovery Institute's Center for Science and Culture
Education
1990 PhD, Chemical Engineering and Materials Science, University of Minnesota, Minneapolis MN.
1984 BS, Chemical Engineering, University of Illinois, Champaign, IL
Personal statement:
I have been studying this subject intensely for about 30 years. My motivation is two-fold. First, the topic of origins is obviously of immense importance. But I think the reason that I have remained so immersed in this subject for so long is that it is tremendously intellectually stimulating to me. I cannot imagine another subject that could be more interesting than understanding what science says about where we, and everything in this universe, came from. I have been fortunate to have had a career as a scientist doing mostly discovery research. Discovering something new about our world, no matter how small, is tremendously motivating to me. As I looked into the science related to questions of origins I came to realize that many of the greatest questions are unanswered and often misrepresented to the public. Digging into that has been incredibly stimulating – it energizes me in a similar way.
I came to faith in God as a professing Christian at a young age. But when I began to study science at the university level and then in graduate school I wanted to understand what science alone says about the origins questions. I am convinced that we must let science be science and allow experimental data to be the arbiter among different views or possibilities. Atheists and people of religious faith both have the tendency to allow their worldviews to bias their interpretations of the data. I have a very high opinion of the Intelligent Design community, especially those at the Discovery Institute, because I am convinced that they understand the role of bias well and work very hard to maintain scientific integrity at all times.
In 2002 and 2003 I organized and co-led a course in the Honors Program at the University of New Mexico titled "Origins: Science, Faith, and Philosophy" with Professor Harold Delaney of the Psychology Dept. The course was presented for two semesters and received favorable reviews from the students that attended. However the course was controversial in the minds of a small number of faculty members who protested to the University provost, and as a result the course was no longer allowed in the curriculum.
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My professional research has covered many areas. I have not had the good fortune of sufficient funding to stay in one general area for my entire career. Rather, the need to secure funding and address the changing needs of government sponsors required me to learn about and explore a wide range of subject areas. While this was demanding in time and energy, it was beneficial to me as I became interested in learning about origins topics in various areas of the physical sciences and biological sciences. For that reason, I include some detail about my present and past research topics below.
Research Topics:
My Ph. D. research topic was to characterize the interactions in polymer blends and copolymers using dynamic and total intensity light scattering and viscometry.
My post-doctoral research topic was the study of the structure of polymers at fluid interfaces using neutron reflectivity and grazing incidence X-ray fluorescence along with Langmuir isotherms.
During my 32 years at Sandia National Laboratories I have been involved with a wide range of research topics in areas including materials science, chemistry, physics, biophysics, and biology. Early in my career I used neutron and X-ray scattering, reflectivity, and grazing incidence diffraction to study the structure of polymers at interfaces pertaining to surface and interfacial properties, water absorption to interfaces for adhesion and interfacial degradation, and mechanisms of action and synergy among cellulase enzymes. Other research topics included the chemistry and mechanics of adhesion and the physical chemistry of wetting.
Another research topic was to understand how the interactions of proteins with lipid membranes affect their activity and function. Many chemistry-of-life processes involve proteins bound to or embedded within membranes where the interaction with the membrane plays a critical role in promoting specific molecular recognition events by altering protein structure. Examples include lipid environments that concentrate integral membrane proteins and facilitate dimerization, and soluble proteins that undergo conformational changes upon inserting into membranes. Understanding such processes requires knowledge of the membrane-induced structural changes in the protein along with characterization of the new ligand binding or enzymatic activities promoted by the structural changes. Due to the integral role that the membrane plays in these processes, standard approaches for studying protein-protein or protein-ligand interactions in solution are not adequate. Moreover, crystallization of proteins in the membrane bound state has proved to be extremely difficult and cannot capture structural transitions that occur as a function of solution conditions or lipid composition. My collaborators and I addressed the need for structural characterization of membrane-bound proteins by combining neutron reflectivity, which provides a mid level resolution profile of residue distribution normal to the membrane, with hydrogen deuterium exchange mass spectroscopy that provides additional information about solvent exposure of the different regions of a protein. We applied this to the study of conformational changes of HIV-1 Nef upon membrane binding by neutron reflectivity and hydrogen-exchange mass spectrometry as it relates to the role of Nef as an adaptor protein to compromise the immune system during HIV infections. Other work included fluorescence spectroscopy and imaging related to the TLR4 receptor in innate immune signaling and the interaction of Dengue virus envelop proteins with lipid membranes as pertaining to mechanisms of virus binding and entry into cells.
While at SNL, I had a co-appointment as a Staff Scientist at the Joint Bioenergy Institute for 15 years where I performed research related to the breakdown of cellulose and lignin using chemical, enzymatic, and microbial approaches.
Another research project was related to antibiotic resistance. It is well known in the antibiotic field that any specific single site on a protein will experience a mutation in 10^8-10^9 organisms and that a typical infection might reach 10^10-10^12 organisms. So treating an infection with a single drug, monotherapy, is bound to fail due to development of mutant strains. The goal of this work was to develop a two drug cocktail where both compounds target a single enzyme, and could possibly be linked together to ensure both are present in the same location and avoid efflux pumps. I worked on acetyl coA carboxylase (ACC) following the work of Grover Waldrop, and in collaboration with him. One compound that inhibits that enzyme is already known so a second compound that inhibits ACC by a different mechanism needs to be found. My group focussed on finding a dimerization inihibitor, as the enzyme must be a dimer to work effectively. Our goal was to develop a dimerization inhibitor based on the fact that dimerization inhibitors were recently discovered for the human version of the enzyme. We performed modeling and in-silico screening of a library of compounds based on displacement of high energy water molecules in the dimerization interface. Then we set up a dimerization assay and began to screen the most promising compounds from the in-silico screen. Unfortunately, the project was derailed by the COVID epidemic and we haven't yet been able to return to it to finish the work.
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For about 5 years I worked on a new idea to use computational modeling combined with experimental library screening to adapt neutralizing antibodies to related virus types and subtypes. The hypothesis behind this work is that adapting known neutralizing antibodies to related virus types and subtypes may be easier than finding and developing an antibody the traditional ways or designing an antibody from scratch. To my knowledge no one has succeeded in using computational modeling alone to redesign antibodies. So my collaborators and I used physics-based and informatics-based molecular modeling to make mutational predictions and then collaborated with a biotech company to do library screening. Together we developed a method to design the library to contain a set of typically 11-12 of the predicted mutations. This might seem like a small number but the library included all the possible combinations and 12! = 480,000,000. Each experimental library contained a few hundred million variants. This approach efficiently distinguishes correct predictions from incorrect predictions. As a first step we used this approach to improve the binding of an existing neutralizing antibody for Venezuelan Equine Encephalitus Virus (VEEV).
Most recently at SNL I was involved in research toward a circular carbon economy and green energy. I led a DOE BETO-funded project in collaboration with Ingevity Corp. and U. of South Carolina to oxidize lignin to generate polymer products such as agricultural dispersants and also to form hydrogels to increase the water holding capacity of soils. I also led a project to develop cost-effective oxidative methods to break down polyolefin plastics into bioavailable compounds for biological conversion to fuels and chemicals. The same approaches are also being applied to the conversion of other waste materials to biogas through anaerobic digestion.
A full list of publications can be found at: https://www.ncbi.nlm.nih.gov/myncbi/16Y2hHddxZekf/bibliography/public/
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