Kenneth V. Mills, associate professor and chair of the chemistry department, has been awarded a $567,000 three-year grant from the National Science Foundation to study the chemical mechanism of protein slicing. Over the last decade, his research projects, which integrate student research participation, have enjoyed uninterrupted financial support from the National Science Foundation bringing in more than $1 million.
His current project is titled “Intein Structure and the Catalysis of Protein Splicing and Hedgehog Autoprocessing: An Integrated Research and Education Program.” Protein splicing is the means by which an intervening polypeptide, or intein, catalyzes its own removal from flanking polypeptides, or exteins. The research program will investigate how the activity of an intein from an extreme thermophile is influenced by its unusual structural stability, how the reaction is catalyzed, how intein activity is regulated, either by temperature or oxidation state, and how splicing is related to the autoprocessing of hedgehog-like domains.
The questions will be addressed by projects amenable to his undergraduates, in collaboration with Chunyu Wang and Saroj Nayak, a structural biologist and computational biologist, respectively, at the Rensselaer Polytechnic Institute.
The research program will have a transformational impact on the careers of Holy Cross research students, says Mills. Students will perform the experiments, present the results at national meetings and in peer-reviewed publications, and, through close mentoring, prepare to be future leaders in STEM (science, technology, engineering and mathematics). The biochemistry concentration will sponsor outreach in the community by hosting lectures aimed at broad audiences and by supporting the Science Ambassadors student outreach program. The program will broaden access to STEM by recruiting local students to the lab through the Worcester Pipeline Collaborative and by educational outreach at a Worcester elementary school.
During his 11 years at Holy Cross, Mills has mentored 35 undergraduate students in research, all but five for multiple years. His lab has produced 20 publications since 2001 with 19 undergraduate student coauthors, including 12 peer-reviewed publications, one technical note, and five review articles.
Of his 27 graduates through 2012, six have started Ph.D. programs in biochemistry or chemistry, five of whom are female. One has finished her Ph.D., another finished a master’s degree and works in industry, and the others are still candidates. Ten students have their medical or osteopathic medicine degrees or are in medical school and another is in a veterinary medicine program. Two are applying to health programs, five are in industry positions, one is a patent attorney and two are in teaching.
Mills’s students have made 33 presentations at national meetings of the American Society for Biochemistry and Molecular Biology or Protein Society, and all of his students in the past nine years have attended a national meeting.
“I attempt to provide research university-like opportunities within the supportive environment of a small liberal arts school,” Mills wrote in his proposal to NSF. “We have weekly group meetings, with everyone presenting their weekly work and one student presenting a research article or other assignment. They learn to troubleshoot, solve problems and analyze data. The students travel to national meetings and prepare their own posters. We have weekly departmental seminars, and I ensure that at least three a year are biochemical. … My students are my most important impact and their successes bring me the most pride of my professional work.”
A resident of Holden, Mass., Mills has been a member of the Holy Cross faculty since 2001. He earned his Ph.D. in chemistry and chemical biology at Harvard University. In 2005, Mills received the National Science Foundation’s CAREER grant for CAREER: Alternative Mechanisms of HINT Domain Autoprocessing: An Integrated Undergraduate Research and Education Program.” He is the co-chair of the biochemistry concentration and has served as a member of the Academic Affairs Council and the Curricular Review Steering Committee.
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