The Power of Collaboration

Students in Dr. Kauwe’s laboratory work with professionals to find a cure for Alzheimer’s disease.

By Dr. John Kauwe

 

Dr. Kauwe with students
From left to right, Cameron Schmutz, Dr. John Kauwe, Josue Gonzalez, and Caitlin Munger.

Many fields of research in the Brigham Young University College of Life Sciences have reached a point where the most important and difficult questions require resources and data collection on a scale that is impossible for any individual research lab. One such question asks, “What is the genetic basis of complex human diseases like Alzheimer’s?” For the last four years, Dr. John “Keoni” Kauwe’s lab in the Biology department at Brigham Young University has played an important role in collaborative research that has led to the discovery of several Alzheimer’s risk genes1-5. Successful participation in many collaborative groups brings success and notoriety to research efforts at BYU and provides BYU students with unique and exciting opportunities to contribute to the most important scientific questions of the day.

Last year, undergraduate students in Kauwe’s lab were involved in the discovery of a rare variant in the TREM2 gene that increases risk for Alzheimer’s disease1. Students Josue Gonzalez and Cameron Schmutz began genotyping over two thousand DNA samples for the TREM2 variant before the initial paper was published. Their results are the first assessment of the frequency of this variant and the effect on Alzheimer’s disease in a population-based sample. Their research was recently published in the journal Neurobiology of Aging6, and it provides important information that will help clinicians to facilitate better diagnosis and treatment.

Matthew Bailey and David McKean, two undergraduate students in the Biology department, have been involved in Alzheimer’s disease research at BYU for more than three years. As a direct result of BYU involvement in collaborative research efforts, these students have been able to develop and hone skills in data cleaning, formatting, and analysis using some of the largest and most complex human genetics data sets in the world. Bailey and McKean recently assisted in screening over five million genetic variants for effects on cerebrospinal fluid levels of the Alzheimer’s disease–related proteins: tau and beta amyloid. Their contributions to this work are recognized by their inclusion as coauthors on the manuscript that was recently published in the journal Neuron2. This work has received considerable attention from other scientists, including several published commentaries7,8.

Direct involvement in such large, collaborative projects also provides students with the opportunity to develop smaller and more manageable projects that remain relevant to the broader scientific community. In the fall of 2010, Kauwe’s lab published work suggesting that variants in two genes, PPP3R1 and MAPT, change cerebrospinal fluid protein levels and alter the rate of decline in individuals with Alzheimer’s disease. This important finding suggests that manipulating the function of these genes may be a viable therapeutic approach for Alzheimer’s disease.

Dr. Kauwe with students
From left to right, Wayne Latu, Mo Lee, Manti Su’a, and Dr. Kauwe in front.

Undergraduates David Peterson and Caitlin Munger worked for several years to further investigate these variants. Using data from collaborators around the United States, they produced an updated analysis that confirms the relationship between these genes and the rate of decline in Alzheimer’s disease patients9. This research has lent these students credibility amongst professionals that continues to help them in their studies. Peterson’s medical school interviewers took notice of his work related to Alzheimer’s disease, and nearly every conversation during those interviews focused on this research. Peterson says, “Mostly due to my involvement in this research, I was awarded a full-tuition scholarship to the Duke University School of Medicine.” Munger is continuing to work toward her bachelor’s degree in neuroscience and says, “I feel connected to the larger scientific community. Often in college, we get so bogged down with the classes we are struggling through—the next reading assignment, the next test. Having this project helps to remind me why I am going through college—so that I can help to solve the real problems of the world. I love being involved with such an important issue.”

In 2011, Matthew Bailey and David Patty, then undergraduates in the Kauwe lab, were able to experience the benefits of networking firsthand when they participated in an important conference call with other experts from Harvard University, Washington University, and the University of Pennsylvania. Bailey and Patty had been charged with developing a visual way to present data concerning their collaborative efforts on the relationships between the variants and traits—a not-so-simple task that both students stepped up to undertake. During the call, Bailey e-mailed his slides summarizing the data, and the group was able to use them as the basis for the discussion. Bailey regards this as one of his favorite memories of being a student, saying of the experience, “We were able to take time and explain our findings to the leaders of the field. I felt proud of the report we gave.” The collaborators were amazed to hear that two undergraduates had compiled the summary, and they quickly suggested that Bailey and Patty consider working with them for their graduate studies. Bailey began his Ph.D. studies at the Washington University School of Medicine with one of those collaborators this fall.

Strong relationships with collaborators can also provide unique internship opportunities for BYU undergraduates. In the last two years alone, students from the Kauwe lab have worked through the summer as collaborators in Japan, the Netherlands, and Italy. Undergraduate student Michael Peterson, who spent eight weeks as an intern in Japan, says, “This wonderful opportunity has opened many doors for me and has inspired me to make international collaboration a part of my future career plans.”

High-quality, collaborative research is a necessity in the modern scientific world. It accelerates research progress and makes the most exciting and difficult scientific questions tractable. BYU, its faculty, and its students all succeed when each contributes to high-quality, collaborative work. Bailey illustrates these benefits, saying, “I can honestly say that the relationship that I’ve developed with Dr. Kauwe and the connections I’ve made in the fields of Alzheimer’s disease and genetics have changed my life forever. Aside from the countless opportunities for presenting at national and international conferences, I found out firsthand that I was capable, as an undergraduate, to be involved in cutting edge research in the field.”

REFERENCES
1. Guerreiro R, et al. TREM2 Variants in Alzheimer’s Disease. N Engl J Med. 2013 Jan p 117–27.
2. Cruchaga C, et al. GWAS of Cerebrospinal Fluid Tau Levels Identifies Risk Variants for Alzheimer’s Disease. Neuron. 2013 Apr p 256–68.
3. Naj AC, et al. Common Variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are Associated with Late-onset Alzheimer’s Disease. Nat Genet. 2011 May p 436–41.
4. Hollingworth P, et al. Common Variants at ABCA7, MS46A/MS4A4E, EPHA1, CD33 and CD2AP are Associated with Alzheimer’s Disease. Nat Genet. 2011 May p 429–35.
5. Harold D, et al. Genome-wide Association Study Identifies Variants at CLU and PICALM Associated with Alzheimer’s Disease. Nat Genet. 2009 Oct p 1088–93.
6. Gonzalez Murcia JD, Schmutz C, Munger C, Perkes A, Gustin A, Peterson M, Ebbert MT, Norton MC, Tschanz JT, Kauwe JS, and others. Assessment of TREM2 rs75932628 Association with Alzheimer’s Disease in a Population-Based Sample: the Cache County Study. Neurobiol Aging. 2013 Jul 12. Available from: http://www. ncbi.nlm.nih.gov/pubmed/23855982. Accessed: 2013 Sept 24.
7. Ertekin-Taner N. Alzheimer Disease: The Quest for Alzheimer Disease Genes-Focus on CSF Tau. Nat Rev Neurol 9. 2013 July p 368–70.
8. Singleton AB. Finding Risk in All the Right Places. Neuron. 2013 Apr p 207–8.
9. Peterson D, et al. Variants in PPP3R1 and MAPT are Associated with More Rapid Functional Decline in Alzheimer’s Disease: The Cache County Dementia Progression Study. Alzheimers Dement. 2013 May. Doi: 10.1016/j.jalz.2013.02.010.