University of Wisconsin

LA CROSSE

March 24, 2015 Re: Letter of Support for Undergraduate Research and Creativity application of Jonathan Lendrum Dear Review Committee Members: It is with great pleasure that I recommend Jonathan Lendrum for an Undergraduate Research and Creativity Grant. Jon has a strong set of skills, high ambition, and a zeal for the project that he describes in this application. I met Jon several months ago, when he contacted me regarding his interest in researching the relationship between gut function and the glymphatic system that clears metabolites from brain tissues of humans and other mammals. He had this specific project in mind, and had already identified a set of related primary literature articles that he had read closely – all from the last three or four years, as the glymphatic system was previously unknown. The area of research is currently of extremely high interest in neurosciences, where the glymphatic system appears to be critical to the understanding of sleep function, and to the understanding of disease progression in degenerative disorders such as Alzheimer’s Disease. Jon has developed quite a lovely proposal over several months of talking ideas through with myself and with other members of the UW-La Crosse faculty, several researchers from Gundersen Health System, and other students who share his passion for science. He has been tireless. Several members of the UW-L faculty will be active collaborators on his project, including Dr. Barrett Klein (Biology) and Dr. Andrew Berns (Computer Science). Personally, I am very excited about Jon’s project, which addresses a hot research topic in microbiology and biology. I am confident that his project can be accomplished with the support that is available from faculty who have expressed a willingness to collaborate here at UW-L. We have spoken at some length about the time requirements for several parts of his project, and also about the financial support that is needed. The first part of his project will be to observe sleep phase patterns using EEG monitoring through piezoelectric transducers that are built into the cages for housing mice. This technology has been used by several laboratories in the U.S., and it is affordable for us. Dr. Andrew Berns (Computer Science) will be working with us in order to replicate/develop our process for monitoring and interpreting the collected data. This part of Jon’s project, in which he expects to find differences in sleep patterns while comparing animals on normal, probiotic, and antibiotic diets, can be accomplished in several weeks once we have become comfortable with the monitoring equipment. Jon has arranged for a company that manufactures the essential equipment to send functional sample equipment to us so that we can develop our methods before summer begins. A second part of the project is more labor-intensive, which has very different challenges. In this part of the project, the goal will be to examine glymphatic clearance of an introduced tracer molecule, using histological techniques. Brain tissues of animals used in the earlier part of the study need to be collected, then analyzed to determine the level of clearance across control and experimental groups. We will certainly be able to collect tissues and begin the analysis during the course of the summer, but my expectation here is that Jon will continue histological sectioning of brain tissue, data collection and analysis for several months after the summer ends. That is also part of his thinking and has been discussed with likely collaborators. The statistical analysis of histological data is often challenging, and Jon has already begun talking with Dave Reinecke (Mathematics/Statistics) about methods that may be of use. Again, there are not costly equipment purchases that will need to be made for this part of Jon’s project, and there are several likely sources of funds to support the cost for consumable supplies. Jon’s budget request is primarily for funding to support the cost of the mice needed for his study to proceed. These costs have been discussed with UW-L’s Lab Animal Research Facility Manager, Amy Cooper, and costs included in the budget are estimated based on information received from her.

Department of Biology, 1725 State St. La Crosse, WI 54601 Ph: 608-785-8238, Fax: 608-785-6959 www.uwlax.edu/biology

In short, I am very excited about Jon’s proposal, and I am quite confident that, if funded, he will be able to complete this project and present results. A bonus here is that Jon writes very well, and he and I expect that this project will lead to work that is publishable in primary research journals. Please give strong consideration to awarding a grant to this skilled and deserving student, who has put together an excellent, intriguing research project design and a plan of action that produces a very high probability of success. Sincerely,

Bradley Seebach, Associate Professor of Biology

Department of Biology, 1725 State St. La Crosse, WI 54601 Ph: 608-785-8238, Fax: 608-785-6959 www.uwlax.edu/biology