SF424 (R&R) Application Guide for NIH and Other PHS agencies

Other Project Information: Facilities & Other Resources

This information is used to assess the capability of the organizational resources available to perform the effort proposed. Identify the facilities to be used (Laboratory, Animal, Computer, Office, Clinical and Other). If appropriate, indicate their capacities, pertinent capabilities, relative proximity and extent of availability to the project. Describe only those resources that are directly applicable to the proposed work. Provide any information describing the Other Resources available to the project (e.g., machine shop, electronic shop) and the extent to which they would be available to the project. Source: PHS SF 424 (R&R) Forms Version C Application Guide

MSU- General Information

The nation’s pioneer land-grant university, Michigan State University (MSU) is recognized internationally as a top research university. Located in East Lansing, MSU encompasses a 5,200-acre campus with 2,100 acres in existing or planned development, 538 buildings, including 95 academic buildings. These, as well eight medical campuses distributed throughout the state are supported by over 5,100 faculty and academic staff, with >38,000 undergraduates, and >11, 000 graduate and professional students enrolled in the 17 degree-granting colleges at MSU.

MSU is listed among the top 50 universities in the world based on research performance, including publications and citations based on rankings compiled at the University of Western Australia. Michigan State’s global standing as a top-notch research and teaching institution continues to improve. The World University Rankings by Times Higher Education, a London-based publication ranks MSU 82, up one spot from last year. Michigan State University is among the top 100 universities in the world, according to a new set of rankings from U.S. News & World Report. According to the rankings, which list the top 500 universities in the world, MSU is tied for 75th with the Netherlands’ Leiden University. This is the first time U.S. News & World Report has rated universities on a global scale. It used a new set of criteria, with a heavy emphasis on the schools’ research prowess. For example, The Institute for Scientific Information included 27 MSU faculty members on its most recent list of "Highly Cited" researchers. Individuals on the list are among the top 250 researchers worldwide in their respective fields in terms of the number of citations to research published and represent about half of 1 percent of all researchers in the sciences and social sciences.

Funding for externally sponsored programs comes primarily from federal agencies, state agencies, industry associations and foundations, with ~$528 million in external funding in 2013-14. As a result, MSU is a member of the prestigious Association of American Universities, a group of only 60 U.S. and two Canadian universities widely regarded as among the top research-intensive institutions in North America.

MSU is the only university in the country with on-campus medical schools graduating allopathic (MD) and osteopathic (DO) physicians, as well as veterinarians (DVM), that each also produce dual- degreed, PhD graduates as well. The College of Nursing is also one of the top research Nursing Colleges in the country. Significant research infrastructure exists to support the research and training efforts underway within each of these colleges.

Basic and T0 level research has been foundational to the successes of the 4 health and medical colleges as they jointly benefit by sharing several distinguished basic sciences departments and their research faculty. These include research faculty in the departments of Physiology, Biochemistry & Molecular Biology, Microbiology and Molecular Genetics, Pharmacology and Toxicology, as well as Epidemiology and others, each again shared with other Colleges including Engineering (COE), the College of Natural Sciences (CNS), and the College of Agriculture and Natural Resources (CANR).

As but one example of several, the College of Natural Science at Michigan State University is home to 27 departments and programs in the biological, physical and mathematical sciences. The college averages $28 M

in research expenditures annually while providing world-class educational opportunities to more than 5,000 undergraduate majors and nearly 1,000 graduate students.

MSU- Community Setting:

The concept of “clinical and translational science” implies that extensive interaction with communities will take place for its implementation. The Agricultural College of the State of Michigan, precursor of Michigan State University, was chartered in 1855 as the nation’s first land-grant institution of higher education. The outreach mission of the University was expanded by the Hatch and Smith-Lever Acts creating a series of Agricultural Experiment Stations and the Cooperative Extension Service, with missions of Outreach and Service to the residents of Michigan. Implementation of this mission at MSU led to establishment of the MSU Extension Service (MSUE) with branches in all of the 83 Counties of Michigan.

For 45 years, MSU, through its distributed Health Campuses, has been educating medical students and nurses in the communities of the State of Michigan. MSU’s three human health sciences colleges (Human Medicine, Osteopathic Medicine and Nursing) have an education system where students begin study in East Lansing or Grand Rapids and move to community health campuses to complete clinical training. Over 50% of the graduates from these colleges remain in the state for postgraduate training and clinical practice, often in primary care, many in underserved regions of the state. These and other strengths, including over 5,000 clinical faculty statewide, have established MSU as a national leader in community-based medical education. MSU recognized early the opportunity to build on its dual foundations namely the MSUE and the three human health sciences colleges, and in 2008 created the MSU Clinical and Translational Sciences Institute (MSU-CTSI).

Community Reach and Population Diversity: MSU’s four health sciences colleges are intimately connected with urban and rural populations of Michigan, as well as with professionals delivering health care to these communities. MSU-CTSI will employ MSU’s existing teaching and hospital networks (Table 1) in the statewide Zones of Research Engagement to implement its clinical and translational science mission (Grand Rapids, Flint, Midland, Detroit area, Lansing, Traverse City region, and Marquette region). The population potentially impacted by MSU-CTSI includes approximately 4.7 million people and is quite diverse, as noted in Table 2.

Clinical and Translational Sciences Institute (MSU-CTSI)

In August 2008, the Michigan State University established the Clinical and Translational Sciences Institute (MSU-CTSI), recruited a Director for the Institute, consolidated existing infrastructure resources, and invested new funds to support the CTSI mission. The MSU Office of Clinical Research (OCR) and the Biomedical Research Informatics Core (BRIC), two independently reporting units, became divisions within the CTSI at that time. MSU-CTSI is strongly linked to the leadership of MSU, and its Colleges and its external partners. The goal of the MSU-CTSI is to develop clinical and translational research infrastructure to the benefit of the communities and investigators in the MSU partner network, and ideally to expand this network by linking with CTSA recipients across the nation. All MSU faculty members or members of partner institutions involved in clinical and translational research and/or teaching may participate in and derive support from the MSU-CTSI. Faculty members and other participants retain their departmental and college affiliations, but the MSU-CTSI adds sustainability and organization to the interdisciplinary and collaborative nature and relevance of clinical and translational research.

MSU-CTSI serves as the multi-disciplinary infrastructure to support MSU clinical and translational research. CTSI is directed by Dr. Andrea Amalfitano, DO, Ph.D, Osteopathic Heritage Foundation Professor, who took on this role in August of 2013. His background in medical practice, genetics research, and clinical research has provided new expertise into an already diverse group. The Director of MSU-CTSI reports directly to the Office of Dr. Stephen Hsu, the Vice President for Research and Graduate Studies, (OVPRGS) who reports directly to the President’s office of MSU, Dr. Lou Anna K. Simon. MSU-CTSI is supported by general fund dollars through the OVPRGS. Investigators engage the support of MSU-CTSI from numerous origins including the human health colleges, basic biomedical disciplines, the social sciences, the College of Veterinary Medicine, and the community.

MSU-CTSI and the divisions of OCR and BRIC are located West Fee Hall at MSU Main Campus in East Lansing. The space accommodates approximately 40 individuals in 6,731 square feet of recently remodeled space. The space has 4 conference rooms, 8 areas of cubicle space with 6 stations each organized on the perimeter of an open common area, and 11 private office suites located on the perimeter of the space. In addition Translational Research Support Facility (TRSF) space in West Fee Hall is currently available in support of clinical research projects. Plans are underway to relocate and expand the TRSF in 2015. The layout of the MSU-CTSI space is below.

Office of Clinical Research Division (OCR): The Office of Clinical Research was established in 2006 to serve the need for enhanced support of clinical and translational research, and to expedite the research administration process. OCR has as its mission to assist researchers with the development, implementation, management, and completion of industry- and government-funded clinical research conducted through MSU and community partners. OCR offers clinical research support services to investigators including feasibility assessment, subject recruitment planning, clinical research coordination, regulatory support, connection to external resources, and access to the local Translational Research Support Facility (TRSF) resources. Serving as the ‘Researcher Advocate’, OCR helps faculty and staff navigate the MSU clinical research environment and facilitates use of tools such as ResearchMatch, StudySearch, and eagle-i. ResearchMatch is a national web-based volunteer registry that connects people interested in participating in research, with researchers looking for participants. StudySearch is an online tool that serves as a central repository of local research studies that are open to enrollment through MSU. Eagle-i provides researchers access to discover needed core laboratory services, reagents, animals, specimens, etc. that are available on campus and nationally. OCR currently serves as the point of contact for linking investigators (both locally and in the community) to existing MSU scientists, research support, and community network resources.

Translational Research Support Facility: The MSU-CTSI TRSF currently consists of two well-equipped outpatient exam rooms, several separate areas for interviewing and study monitoring, secured space for record and drug storage, several blood collection areas, and a specimen processing laboratory. Exam room equipment includes infusion chairs, ECG machines, and other various equipment needed to complete physical examinations. The specimen processing laboratory equipment includes multiple benchtop centrifuges (refrigerated and portable) and multiple temperature-monitored refrigerators and freezers for drug sample storage. The TRSF and staff are a registered vaccination clinic through the Michigan Care Improvement Registry. Plans are underway for a major expansion of space and services for 2015 to accommodate the increased need for research-dedicated clinic space, as well as to better meet the needs of research participants.

Biomedical Research Informatics Core Division (BRIC): BRIC was established by MSU in 2001 as part of the University’s commitment to strengthen informatics and research IT support for clinical and translational researchers. The unit provides pre-award consultations and assistance with data management plans and budget, as well as post award support to investigators for a variety of data capture, data security, and study management services. BRIC provides strong support for observational studies for both internal and external investigators, working closely with data analysis collaborators and the investigator’s team members.

BRIC provides best-in-class informatics support of the operation and administration of the MSU-CTSI. This includes research information databases and web sites to provide information and to foster communication among MSU clinical and translational investigators. BRIC provides a risk-based security management system focused on the confidentiality, availability and integrity of data. It has an active program to insure compliance with HIPAA and other federal and state laws and regulations as they pertain to data matters. BRIC reduces barriers to the initiation of new research projects while maintaining high standards of clinical research informatics by providing access to scalable and affordable informatics tools for pilot or early stage research; eliminating cost barriers to high level informatics by offering no or nominal charge licenses to new investigators or seasoned investigators beginning internally funded new lines of research; providing training and support to assure implementation of systems relatively trouble free; using informatics solutions to reduce technical obstacles to research initiation. Faculty and staff of the Biomedical Informatics Core (BRIC) help ensure that data are accessed under safe and compliant conditions.

Consortium of Academic Programs in Clinical Research (CoAPCR): MSU-CTSI and the Program in Public Health represent MSU as a member of CoAPCR. CoAPCR is comprised of global educational institutions offering academic credit in all areas of clinical research, regulatory affairs, and clinical data management. In addition, a supporting membership is available to organizations that are stakeholders of students graduating from clinical research academic programs, and to other organizations that are related to the clinical research enterprise, dedicated to enhancing the quality and safety of the clinical research enterprise through education and training. CoAPCR facilitates the development of high-quality educational programs encompassing all areas of clinical research that are based in academic credit-granting institutions. CoAPcR, as a member of the Joint Task Force for Clinical Trial Competency (JTFCTC), produced the 8 domains of the harmonized core competencies for the clinical research professional. CoAPCR’s mission is to 1) provide a medium for communication among educators of clinical research professionals, 2) encourage and support the development and maintenance of academically based clinical research educational programs to meet the needs of the clinical research community, 3) foster inter-institutional articulation among educational institutions, clinical institutions, professional associations, and industry, 4) initiate and/or support research and studies relating to the educational, manpower and service needs of clinical research professionals.

Institutional Partners of the MSU-CTSI:

MSU is unique among American universities by having 4 health colleges (3 human, 1 animal science school): CHM, COM, CON, and CVM. These colleges were established with major missions to train community-based clinicians, whose primary focus is the care of patients/animals in the communities of Michigan. For clinical education and training, CHM, COM and CON partner with regional hospitals across Michigan. After training, these health care professionals continue to serve in smaller cities, towns and rural underserved areas. The basic sciences education and research at these colleges are based at MSU’s central campus in East Lansing.

CHM In addition to 4-year medical schools in East Lansing and Grand Rapids, the CHM uniquely provides students with comprehensive training in clinical settings that most closely parallel the environment in which many physicians practice. During the third and fourth year of the CHM program (Block III), students complete a series of required and elective clerkships at one of MSU’s seven community-based program sites, located in Flint, Grand Rapids, Kalamazoo, Lansing, Saginaw, Traverse City and the Upper Peninsula. Each community program is aligned with area hospitals and outpatient facilities that join MSU in creating a rich educational environment for students. Several sites have residency programs in various specialties, as well as fellowship programs (cardiology, hematology/oncology, endocrinology, infectious disease),

The CHM MD/PhD programs are well-integrated training programs that combines medical training (MD) with outstanding graduate training, leading to PhDs in areas of biomedical research (East Lansing, Grand Rapids). Community Associate Deans for education and research live in their respective communities, but meet regularly as a group and thus are a potential link to research conducted in each of the communities. Although most community health campuses have research offices that assist investigators to perform and present their research, all do not have access to needed resources, particularly statistics and bioinformatics, and few have NIH funding or mentors.

COM was the first college of osteopathic medicine at a major university in the US, and for the 14th year, the MSU College of Osteopathic Medicine was named as one of the nation’s top colleges for educating primary care physicians by U.S. News & World Report’s annual rankings of the best graduate schools. MSU was the first osteopathic school to offer the “DO/PhD” dual-degree program. COM’s Statewide Campus System comprises 30 hospitals; education directors in each hospital communicate directly with one another several times a year. With this leadership position, and the maturation of the Osteopathic profession, COM is actively growing its focus and investment in clinical and translational research, a transformation that is strongly assisted by the MSU-CTSI.

CON’s community sites serve as education sites for baccalaureate students including accelerated second degree students, Masters of Science in nursing, Certificate programs for nurse practitioners and clinical specialists in education, as well as a PhD in nursing. The nursing programs are consistently rank high by the U.S. News & World Report, with online graduate nursing programs ranking # 31, up 15 spots from 2013.

Masters and baccalaureate students train in approximately 120 community sites that include hospitals, physician offices, health departments and schools. CON tenure track faculty are research intensive with the goal of achieving funding for community based research such as chronic health conditions and health in families and populations. Current research funding sources include NIMH, NINR, .NCI, NHLBI, USDA, foundations, the state of Michigan, and other agencies.

CVM provides clinical services and education on MSU’s East Lansing campus. The college has expertise in public health, biomedical and comparative medical research, ecosystem and environmental management, and the multiple facets that compose our complex global food system. Comparative Translational Research between human and animal disease states provides a unique opportunity to Universities with both human and animal health colleges. MSU is particularly well poised to excel in this area due to the highly integrated nature of the laboratory science departments across all the health colleges, a focus on how molecular and cellular events integrate into whole-animal function in health and disease, and several strong research foci in CVM, including oncology, cardiology, ophthalmology, pain management, and respiratory syndromes. CVM will contribute to the MSU-CTSI mission through its education and research programs on how molecular and cellular events integrate into whole-animal function in health and disease, and in the use of appropriate animal models to study human and animal disease.

In 2004, health care, research, education and business leaders in Grand Rapids, the second largest city in Michigan, collaborated and assisted MSU’s College of Human Medicine to expand its campus to West Michigan. The vision was to solidify the existing long-term partnership between MSU CHM and Grand Rapids health care institutions, to establish a research enterprise, and to train a new cadre of physicians and researchers in clinical translational science, all quite consistent with the vision of the MSU-CTSI. The office of the Dean of MSU CHM is now located in Grand Rapids.

MSU Extension: For the past 100 years, MSUE has been continuously interactive with urban and rural communities of Michigan in all 83 counties of the State. The activities of the MSUE offices are community-centered, needs-focused, inclusive, accessible, and collaborative. Strategic sessions, held yearly in the communities, ascertain the most important needs of the community, which are then used to recruit MSU researchers to address these needs. MSU has taken the unique steps of placing tenured track and other research faculty physically in existing sites in Michigan in the Community Based Health Initiatives Sites (CBHRI). This is an expansion of MSUE health education programs, run by county-based educators (CER Research Liaisons with Master’s Degrees or PhDs), as well as by MSU on-campus faculty, on: [a] nutrition, food preparation, food safety; [b] chronic disease management; [c] early childhood development; and [d] public health. These grass-roots, stable connections to communities across the State allow us to employ this effective and community-engaged CBHRI network to assist the MSU-CTSI to reach into our communities to understand their health concerns and bring these back to the MSU-CTSI and then assist in jointly designing research to address these concerns with the communities themselves. MSUE was part of significant NIH funded projects such as the National Children’s Study (Paneth, PI HHSN2672007 00034C and HHSN275200800007C). Hence, the inclusion of CBHRI through MSU Extension as a central component of the MSU-CTSI represents an opportunity to establish a model for translational research collaboration in the community that can be replicated by other CTSA funded entities throughout the nation.

University Outreach and Engagement (UOE): MSU’s UOE creates University-Community collaborative to bring the benefits of University knowledge to the public and to address priority issues of concern to society. To date, these activities have not addressed clinical and translational research. UOE will assist MSU-CTSI to reach out to Michigan’s communities and engage them in relevant clinical and translational University-Community team-based research. The Carnegie Foundation for the Advancement of Teaching selected MSU in 2007 as one of the first universities to be designated as a “Community-Engaged University”. Additional information about UOE is noted under the Translational Science Base, Community Engagement Resources and Facilities.

Community-based Research Networks:

Great Lakes Research Into Practice Network (GRIN): The Great Lakes Into Practice Network (GRIN) practice-based research network, a long-standing collaboration between MSU and University of Michigan, combined three networks: [1] Upper Peninsula Research Network (UPRNet) (established in1988), a rural primary care research program of MSU CHM’s Department of Family Practice, in the State’s northern territories; [2] Michigan Research Network (MIRNet) (established in 1984) co-funded by MSU, Wayne State University and the University of Michigan involving urban and suburban health care practices in small towns and rural locations; and [3] Primary Care Research Network (PCRNet) (established in 1985), a joint program of MSU’s CHM and CON, which includes family practice, internal medicine, pediatrics, obstetrics/gynecology, and nursing. The networks merged in 2000 to form GRIN. GRIN also has a collaborative relationship with MetroNet, a practice-based research network comprising urban practices in the Detroit area created by the Department of Family Medicine at Wayne State University Medical School. To date, over 149 practices have actively participated in a GRIN study. The practices are evenly distributed between large, medium and small cities; about one-half of the physicians have an academic affiliation with MSU. The patient population served by GRIN is comprised of 13% African-Americans, 71% white, 5% Hispanic, 3% Asian, and 6% other. In 2013, GRIN included $13 million in funded on topics ranging from diabetes prevention and self-management (PI: Holtrop at MSU Department of Family Medicine) and patient preferences for office visit summaries (PI: Dontje at MSU College of Nursing).

Institute for Health Policy: The mission of the Institute for Health Policy is to improve the health care available to Michigan residents through research, policy analysis, education and outreach, and support of quality improvement activities. The Institute achieves its mission by an ongoing commitment to health services research, quality improvement, and health policy. The Institute for Health Policy works closely with the Michigan Department of Community Health, Michigan Medicaid managed care plans, professional organizations, and community-based agencies on collaborative projects to improve health care delivery in Michigan. IHP supports and conducts health research and analysis by MSU faculty on issues of quality of care, access to care, health disparities, and other topics impacting Medicaid, the underserved, and other populations; conducts health policy analyses to assist decision makers at state, local, and national levels; provides quality improvement technical assistance and support to Michigan Medicaid managed care plans and the Michigan Medicaid program; and offers workshops, educational seminars, and web-based education for various audiences and participates in educational functions offered by other MSU colleges and organizations.

BIG 10 Cancer Research Consortium (BTCRC): The Big Ten cancer centers have united to transform the conduct of cancer research through collaborative, hypothesis-driven, highly translational oncology trials that leverage the scientific and clinical expertise of Big Ten universities. The goal of the Big Ten Cancer Research Consortium is to create a unique team-research culture to drive science rapidly from ideas to treatment-changing paradigms. Within this innovative environment, today’s research leaders collaborate with and mentor the research leaders of tomorrow with the unified goal of improving the lives of all patients with cancer. MSU, via the Breslin Cancer Center, is a member of the BIG-CRC, a consortium that includes several CTSA designated hubs. Additionally, Michigan cancer patients now have greater access to new and unique clinical trials, as a consortium of eleven hospitals and research institutes in 2014 were designated by the NCI as a NCI- Community Oncology Research Program (NCORP). CRCWM members include MSU, VARI, the Mercy Health-Mercy Campus, Munson Medical Center, Spectrum Health, and the West Michigan Cancer Center.

Cancer Research Consortium of West Michigan (CRCWM): Grand Rapids Clinical Oncology Program (GRCOP) initially formed to develop community cancer patient management guidelines. In 1983 GRCOP changed its focus to become one of the first participants in the National Cancer Institute (NCI) Community Oncology Program (CCOP), offering national clinical trials through a community-based clinical research program. On August 1, 2014 with the support of a National Cancer Institute Clinical Oncology Research Program (NCORP) Grant, Grand Rapids Clinical Oncology Program and Kalamazoo Community Clinical Oncology Program joined together to form a new program: Cancer Research Consortium of West Michigan (CRCWM). CRCWM offers local access to and data management support for over 150 cancer research studies. CRCWM works with local hospitals and cancer organizations to provide the highest quality care for cancer prevention and treatment. CRCWM continues to provide access to the latest cancer research both nationally and locally.

MSU Collaborating Hospitals:

Collaborating hospitals and institutes will work within the MSU-CTSI to provide the resources necessary for a “distributed” clinical and translational research and training enterprise. The MSU-CTSI through the MSU Health Colleges – has affiliation relationships with 51 hospitals across Michigan who collaborate in research and education (see Table 1). The Spectrum Health / MSU CHM Alliance in Grand Rapids provides access to the largest tertiary care center in West Michigan; within this Alliance, over 800 clinical studies are in progress annually. The agreements with Sparrow Hospital in Lansing and McLaren Health Care, Inc., in Southeast Michigan, commits the resources of the hospitals and MSU CHM, COM and CON to collaborate in both clinical practice and research areas. In addition, Marquette General Hospital in the Upper Peninsula and key hospitals in Flint, Saginaw and Detroit provide critical opportunities for clinical and translational research.

MSU Facilities/Institutes/Centers of Particular Interest:

The Department of Biomedical Engineering: The Department of Biomedical Engineering (BME) was approved by the MSU Board of Trustees on Oct. 24, 2014, opening the door for collaborative health care related research between the college and rest of campus. The effective date of unit is January 1, 2015, and the first courses in the new department will be offered in Spring 2016. The new department will become a focal point for technological innovations in healthcare technology applied to the medical needs identified by physicians, nurses, and health scientists in hospital, clinic, and home settings. The department will be uniquely positioned to bring technological innovations to the vast state-wide network of healthcare providers served by the University. Biomedical engineers will work in concert with a variety of MSU colleges, including: Human Medicine, Osteopathic Medicine, Nursing, Natural Science, Social Science, and Communications Arts and Sciences. Advantages will include: leveraging expertise from diverse disciplines across campus; working together to provide cost efficiencies; mutually advancing emerging health science discoveries; helping to improve health care accessibility. Samples of neuro-electrical interfaces include: support neuroscience research and therapy; imaging enhancement technologies; robotics for physician assistance; sensors to assess the health of patients in home settings.

Bioengineering Facility: Many of the new Biomedical Engineering department's activities will be centered in the MSU Bio Engineering Facility, currently being built on the south side of campus. The almost $61 million project has four stories and around 130,000 square feet. Faculty members are expected to start moving into the new structure in summer or early fall 2015. Its primary tenants will be faculty members from MSU's colleges of Engineering, Human Medicine, and Natural Science. The construction of the Bio Engineering Facility will provide a unique opportunity to bring together research teams from engineering and biomedical research to promote the development of bio-engineering and engineering health sciences at Michigan State University. These emerging research areas have significant opportunities for increased federal research funding, as well as for technology transfer to the private sector, which can promote the development of a transformational bio-based economy in Michigan.

Collaboration between researchers from different disciplines, ranging from chemical veneering, electrical engineering and mechanical engineering to pharmacology, physiology and radiology, will be essential in the development of new areas of research such as tissue engineering. The new laboratory space will provide research capacity necessary to support new hires and funded researchers in the area, and allow collaborators from different academic units to be co-located. Faculty from the College of Engineering, College of Human Medicine and the College of Natural Science will be the primary occupants of the building. Additional benefits will be realized with the placement of the Bio Engineering Facility adjacent to the Clinical Center, Life Sciences, and Radiology buildings.

Institute for Quantitative Health Science and Engineering (IQHSE): Housed in a state-of-the-art, 130,000-square-foot, four-story Biomedical Engineering facility slated for completion in the Fall of 2015, the Institute is an inter- and multi-disciplinary research center devoted to basic and applied research at the interface of life sciences, engineering, information science, and other physical and mathematical sciences. In a collaboration of the Colleges of Engineering, Human Medicine, and Natural Science, and drawing on the existing research strengths of an AAU, Tier One public research university, the Institute will serve as a magnet to attract talented

researchers and will enhance the growth potential of the University as a whole. MSU envisions a research core of at least 20 collaborators in the Institute, recruited to the University specifically to build capacity in the areas of: computational genomics, proteomics, and other related fields; neuroscience and imaging; and data science related to drug discovery and complex health modeling. 

Grand Rapids Biomedical Research Center: Michigan State University Board of Trustees has authorized the MSU administration to proceed with demolition of the former Grand Rapids Press building located in downtown Grand Rapids on property the university acquired in 2012. The building to be razed is on a site of approximately 4.3 acres, positioned immediately west of the Michigan State University College of Human Medicine’s Secchia Center. The budget for this project (demolition) is $3 million. Funding will be provided through the university’s general fund and tax-exempt financing with debt repayment from a variety of sources including the general fund. Demolition is scheduled to begin in March 2015, with final completion of demolition by December 2015.At a future MSU Board of Trustees meeting this winter, the MSU administration plans to recommend construction of the Grand Rapids Biomedical Research Center on a portion of this site. The remainder of the site may be divided into parcels for future development by the university and/or private developers. Pending approvals, the new Grand Rapids Biomedical Research Center is planned to open late 2017.

The Grand Rapids Biomedical Research Building will allow the College of Human Medicine to advance its trajectory of NIH-funded research growth. In 2010, MSU College of Human Medicine opened the Secchia Center, a $90 million privately-funded facility constructed specifically for medical education and not designed to accommodate research laboratories. This was part of a long-range strategy that involved MSU partnering with Van Andel Institute and Grand Valley State University to lease laboratory space to support new NIH-funded researchers recruited to Grand Rapids. Through December 2014, the medical school has recruited 18 principal investigators (PIs) and their scientific teams to West Michigan and now fully occupies all desirable laboratory space available to MSU in Grand Rapids. Over the next two years, college anticipates recruiting another 6 to 9 additional PIs, for a total of 24 to 27 – plus their research teams. Demolition is scheduled to begin in March 2015, with final completion of demolition by December 2015. Pending approvals, the new Grand Rapids Biomedical Research Center is planned to open late 2017, and will have 145,000 sf of research space.

Renovation of Flint Campus Medical Education and Public Health Research Facility: As a result of the ongoing community engagement in the economically depressed city of Flint, Michigan, CHM is renovating a new 40,000 square foot facility, dedicated to pursuing the health and societal questions being raised by the citizens of Flint, and now being addressed by the research faculty physically placed in those locations. The medical school’s expansion was made possible by more than $11 million in grants from the Charles Stewart Mott Foundation and the ongoing medical education support by MSU’s hospital partners Genesys Regional Medical Center, Hurley Medical Center and McLaren Flint. MSU’s new research and learning spaces include shared student space, four student study rooms, six clinical skills examination rooms, the college’s Flint campus suite, offices for the program in public health and workstations to house six public health principal investigators and their research teams. Over the next six months, more than 20 faculty and staff from the college are moving into the new space, with room for additional people planned.

National Superconducting Cyclotron Laboratory (NSCL): NSCL is a world-leading laboratory for rare isotope research and nuclear science education. With support from the U.S. National Science Foundation, the laboratory operates as a national user facility that serves more than 700 researchers from 100 institutions in 35 countries. Major contributions have been made in the fields of nuclear structure, nuclear astrophysics, heavy-ion reaction mechanisms, accelerator physics, beam dynamics and experimental techniques. NSCL also is the source of innovations that improve lives. A medical cyclotron built by the laboratory in the 1980s was used to treat cancer patients at Harper University Hospital in Detroit for more than 15 years. More recently, NSCL technology and design concepts were used in a new, higher-powered medical cyclotron built by Varian Medical Systems. The collaboration agreement, an example of technology transfer that returns benefits to the university, will bring more advanced nuclear therapy to cancer patients in several countries. In mid 2009, Michigan State University and the Department of Energy Office of Science signed a cooperative agreement to design a build a new $550 million Facility for Rare Isotope Beams (FRIB).

Facility for Rare Isotope Beams (FRIB): The U.S. Department of Energy has selected MSU to design and establish the Facility for Rare Isotope Beams, also known as FRIB, a facility that will advance understanding of

rare nuclear isotopes and the evolution of the cosmos as it provides research opportunities for scientists and students from around the globe. A world leader in rare isotope research, Michigan State has been committed to advancing accelerator-based sciences for more than 50 years. The Facility for Rare Isotope Beams (FRIB) will be a new national user facility for nuclear science, funded by the Department of Energy Office of Science (DOE-SC), Michigan State University (MSU), and the State of Michigan. Under construction on campus and operated by MSU, FRIB will provide intense beams of rare isotopes (that is, short-lived nuclei not normally found on Earth). FRIB will enable scientists to make discoveries about the properties of these rare isotopes in order to better understand the physics of nuclei, nuclear astrophysics, fundamental interactions, and applications for society. The FRIB resource is available to power advanced biomedical research as well.

BEACON: MSU is home to BEACON, one of five highly coveted National Science Foundation Science and Technology Innovation Centers. The Bio/computational Evolution in Action Consortium brings together biologists, computer scientists, and engineers to study evolution in both natural and virtual settings and apply knowledge to real-world problems, including those affecting health. BEACON capitalizes on the existing research facilities and equipment of its members to optimize services and experiences for all participants. We describe below some of the institutional resources that are heavily used by BEACON members at each of our partner institutions. In addition, all faculty members maintain their own laboratory and/or computing facilities, which are not described here.

MSU provided a Center office complex for the establishment of BEACON Headquarters, which houses the director, deputy director, managing director, education director, diversity director, administrative assistant, accounts manager, and information technologist, as well as 5 shared offices for faculty, postdocs, and visiting scholars, and desk space for up to 16 graduate students. The BEACON Center has a seminar room with Polycom and Tandberg dedicated videoconferencing equipment, augmented by a central "bridge" at MSU (outside BEACON). Presenters are able to speak and show slides at any of the partner schools and have them viewed at high quality at the other universities. The Center also has a conference room that seats about 15 people with a large wall-mounted monitor and videoconferencing capabilities. The university has committed to finding additional headquarter space for BEACON’s second phase so that we may house more graduate students and postdocs and have temporary space for collaborators from industry.

Center for Advancing Microbial Risk Assessment (CAMRA): MSU is the leader in a research project funded by a $10 million grant from the U.S. Environmental Protection Agency and the Department of Homeland Security to create the Center for Advancing Microbial Risk Assessment, a consortium of scientists from seven universities with expertise in quantitative microbial risk assessment methods, biosecurity, and infectious disease transmission through environmental exposure. CAMRA is a consortium of international scientists, researchers and students who are interested in risk assessment for microbial agents and control of infectious diseases. The vision of CAMRA is to be the global international collaborative for QMRA. The mission of CAMRA is to provide a network that can link to critical data for running a QMRA, educational opportunities for QMRA and QMRA case studies.

Diagnostic Center for Population and Animal Health (DCPAH): Relative to animal studies and translational research, MSU's Diagnostic Center for Population and Animal Health (DCPAH) is one of the country's premier and busiest veterinary diagnostic laboratories. From just over 9,700 cases when it first opened in 1973, the facility now handles more than 200,000 cases and more than 1.2 million diagnostic tests per year. DCPAH is a full-service veterinary diagnostic laboratory offering more than 800 tests in 11 service sections. In the more than 30 years since its inception, DCPAH has become one of the country's premier veterinary diagnostic laboratories, handling more than 220,000 cases involving approximately 1.5 million tests annually. The Michigan State University Diagnostic Center for Population and Animal Health is an invaluable professional resource, making quality, trusted, and comprehensive veterinary diagnostics widely available. Income from the laboratory is reinvested in teaching, research, and outreach for the purpose of protecting human and animal welfare domestically and around the world.

MSU Center for Ethics and Humanities in the Life Sciences (CEHLS): CEHLS has established bioethics curricula for CHM, COM, CON and CHM students at MSU. CEHLS has 10 interdisciplinary faculty members with degrees in philosophy, medicine, law, social sciences, and health services research. Faculty expertise of includes the law and ethics of human subjects research, community perspectives in developing policy related to emerging genetic knowledge; the ethical and social pitfalls in trying to use scientific evidence to shape

clinical judgment and practice; the effects of cultural differences in communicating complex new knowledge to patients, in managing illness, and in designing health research; and interventions to improve patients’ understanding of and participation in decisions about complex medical choices. CEHLS administers the Medical Ethics Resource Network of Michigan (MERN), a consortium of institutional ethics committees and individuals active in research and clinical ethics around the state. MERN can provide a medium for developing large-scale, multi-site studies that extend beyond the clinical campus communities.

MSU In Vivo Facility: This facility is a contract research organization serving academic and industry clients while housed within Michigan State University. We enable important life sciences and biotechnology research by providing high quality standard and specialized in vivo pharmacology models, investigative and drug development services, medical device testing, and education. We are distinct from existing contract research organizations in our ability to leverage the collective expertise of a major university. The MSU In Vivo Facility offers efficient turnaround, competitive pricing, and the ability to connect directly with scientists involved in studies. We routinely develop custom models and evaluations to fit a wide range of research needs. For current Michigan State University faculty and staff, the MSU In Vivo Facility offers a specialized set of services optimized for academic research.

Research Technology Support Facility (RTSF): RTSF Cores provide technical and analytical support for Biomedical and Agricultural research at Michigan State University in Bioinformatics, Flow Cytometry, Genomics, Imaging-IVIV, Mass Spectrometry, and Proteomics. The RTSF Cores and their services are accessible to researchers at MSU and academic and research institutions throughout the world. Their mandate is also to provide services to all Michigan Biotech and Pharmaceutical Companies, and they have institutional customers from all over the globe. The RTSF consists of 6 cores, described below.

Bioinformatics Core: The RTSF Bioinformatics Core has high powered computers, as well as web-designers, database experts, programmers, and systems administrators who understand biology and biochemistry. Together they can analyze sequence and microarray data, develop a website to make the data available to the general scientific community, and make sure that data on the web is safe from hackers and backed up regularly. One of the hardest tasks in modern research is organizing large data sets from multiple sources, such as might be generated from microarray and proteomic analysis. The RTSF Bioinformatics Core is at the leading edge in designing and developing new data schemas for databases that allow researchers to ask complicated questions and come up with insightful answers. Additional information can be found in the Translational Science Base, Informatics Resources.

Flow Cytometry Core: The RTSF Flow Cytometry Core offers two flow cytometers to the MSU community. Both are multiple laser based optical instruments that analyze cell populations for multiple characteristics simultaneously. Flow cytometry is a laser-based technique that analyzes cell populations in suspension. Flow cytometry analyses can simultaneously detect several biochemical parameters at rates up to thousands of cells per second.

The Influx sorter can detect up to 14 colors with a maximum of 16 parameter.  Forward scatter is collected from a high sensitivity detector unit with resolution slightly below 0.2 um.  The machine can sort up to 4 selected populations.  Sorted cells may be collected into a variety of tubes or plates.The LSR II (Flow cytometer analyzer) can detect 9 colors with a maximum of 11 parameters and is useful for analysis only. All parameters are correlated and analyzed simultaneously. Cells can be characterized simultaneously through the detection of fluorescent probes for nuclear ploidy, cell cycle, apoptotic state, expression of plasma membrane, cytoplasmic and nuclear proteins and other cellular characteristics  The laser excitation lines and common fluorochromes excited are: 1) 488 - FITC, PE, PerCp-Cy5, PE-Cy7.  Other flourochrome combinations are available at the PerCp-Cy5 detector.  2) GFP, YFP or RFP reporter proteins can also be detected. 3) 405 - AmCyan, Pacifici Blue. 4) 640 - APC, Alexa 700, APC-Cy7.

Researchers save their data and analyze it using the Verity software line for post-acquisition data analysis. Both flow cytometers are equipped with digital data acquisition electronics and DIVA data acquisition software.

Genomics Core: The RTSF Genomics Core (MSUGC) provides single gene to genomic scale DNA sequencing services, DNA fingerprinting and genotyping, quantitative PCR, microarray printing and analysis. The MSUGC has been providing genomic services for over a decade. Their mission is to keep pace with the

ever broadening world of genomic technology and make the research process as simple as possible. Services include the following:

NGS Library size selection: The importance of increased read lengths for sequencers is directly proportional to the proper NGS library insert size. Proper reads lengths are extremely important for applications like mate pairs, chip-seq, PacBio preps, miRNA or proper genome sequencing libraries. Agarose gels and beads can only provide so much precision in terms of size for sequencing libraries and are inferior to automated methods for complete accuracy. The Genomics Core can now perform automated size selection accurately using the Sage Science Blue Pippin. This platform uses gel cassettes to provide a full range of size selection options between 90bp up to 50kb.

Cell ID: Short tandem repeat (STR) loci are among the most informative polymorphic markers in the human genome. Additionally, STR profiles help to ensure the quality and integrity of human cell lines within the scientific community as mandated by the NIH. The MSUGC provides cell identification services using the ProMega Cell ID System which employs simultaneous co-amplification and three-color detection of ten loci in a single tube. This kit is designed to run on the ABI 3730xl.

Mouse Genotyping: MSUGC utilizes the Mouse Genotyping kit technology from Kapa Biosystems. Rapid extraction and amplification of DNA from tissue occurs in less than 1 hour followed by state of the art electrophoresis instrumentation for rapid turnaround service.

Sample Shearing:  Preparing high quality libraries for sequencing is paramount for obtaining good data and the majority of protocols require fragmentation of the nucleic acid material to a specific size range. Mis-sizing of the libraries can result in inaccurate quantification, poor cluster density and subsequently low quality data.

Shearing Services: The MSUGC provides shearing services for all NGS library types using the Covaris S2 Adaptive Focused Acoustic Disruptor. This platform enables improved preparation of small biological samples up to 100ul in volume. Applications include DNA and chromatin shearing, tissue disruption and homogenization, and cell lysis among others.

Sample QC: Library construction is the process of taking nucleic acid from its original state to a "library" that can be run on a sequencing platform. Preparing high quality libraries is important for obtaining good data and the MSUGC checks each sample before and after the library construction process to ensure it is of high quality. Concentration, size and quality can be assessed using one of our microfluidics based platforms

Imaging IVIS Core: The RTSF Imaging IVIS Core Facility is the newest core to open to MSU Researchers for quantitative bioluminescent and fluorescent (transmission and reflectance) imaging in vivo and in vitro. The X-RAD 320 is a self-contained x-ray system for delivering radiation dosages safely and effectively to specimens e.g. cell cultures, small animals. The IVIS Spectrum is a light tight imaging chamber with integrated gas anesthesia and heated stage for quantitative bioluminescent and fluorescent imaging in vivo and in vitro. Take advantage of bioluminescent and fluorescent reporters across the blue to near infrared wavelength region using the IVIS Spectrums narrow band excitation and emission filters and spectral un-mixing algorithms.

Mass Spectrometry Core: uses an array of mass spectral techniques for small molecule identification as well as analyses and for Metabolomic profiling. The RTSF Mass Spectrometry and Metabolomics Core is an ‘open access’ resource where MSU researchers and Core staff perform chemical analyses for small molecules and intact macromolecules. The Core features 12 autosampler-equipped mass spectrometers that collectively provide GC-MS, LC-MS/MS, accurate mass (high resolution), and MALDI-TOF capabilities. Analyses performed here typically involve compound identification, quantification, and statistical analysis. Core staff are available to provide expert consultation regarding method development and data interpretation. Students and other researchers are encouraged to become certified users of the instruments; training includes discussions of theory and operation of the Core instrumentation; following training, users are provided 24/7 access to the instruments. Methods currently running include nontarget metabolite profiling (metabolomics) and  high-throughput profiling and quantification of amino acids, phytohormones, nucleotides signaling oxylipins, structural lipids, and central and specialized metabolites. Capabilities for MALDI-TOF tissue and surface

imaging have also been developed. The Core performs analyses of samples from more than 100 institutions from across North America.

Proteomics Core: The MSU Proteomics Facility provides resources to assist researchers in the identification and characterization of proteins and peptides. Experiments from simple protein discovery to complex differential proteome profiling and quantification as well as post-translational modification mapping can be performed using our state-of-the art instrumentation and software.

The MSU Proteomics Facility utilizes the Bio-Rad Criterion size gels (8cm x 11cm; 11cm IEF) for 1D and 2D-PAGE and various pH ranges and precast gel types are available. Gels can be stained with either Colloidal Coomassie, Krypton fluorescent or mass spec compatible Silver stains. Additionally, the facility offers protein and peptide separations in the liquid phase using the Agilent 3100 Offgel Fractionator or the Invitrogen ZOOM IEF Fractionator. Using the Offgel Fractionator proteins/peptides can be separated into 12 or 24 distinct fractions over various pH ranges. For larger protein loads, the ZOOM IEF fractionator can be used to generate up to 7 pH fractions between pH 3 and 12. Any of these fractions can be further used for second dimension SDS-PAGE separations or desalted and analyzed directly on a mass spectrometer.

The MSU Proteomics Facility contains two state of the art mass spectrometers.  The workhorse of the facility is a ThermoScientific LTQ Linear Ion Trap mated to a Waters nanoAcquity UPLC and Bruker/Michrom CaptiveSpray nanospray ionization source.  This machine combines fast, sensitive ion detection and MSn capabilities with exceptional LC gradient stability and resolution for rapid protein and peptide identifications on both large and small scale.  For more specific experiments we also operate a ThermoScientific Q-Exactive mass spectrometer with an attached EASY-nLC UPLC and flex-spray nano-spray ionization source.  This system provides optimized split-free peptide separation, high-performance quadrupole ion selection and high-resolution, accurate-mass (HR/AM) Orbitrap detection for unprecedented peptide detection, characterization and quantification.  Spectral processing, matching and quantification are done using both the Mascot Distiller software suite with the Mascot search algorithm and the MaxQuant/Andromeda software suite.  Results are further validated and visualized using the Scaffold software package.

Medicinal Plant Genomics Resource: Natural products from plants serve as rich resources for drug development with almost 100 plant-derived compounds in clinical trials in 2007. Plant derived natural products have had a profound and lasting impact on human health and include compounds successfully used for decades such as digitalis, Taxol, vincristine, and morphine isolated from foxglove, periwinkle, yew, and opium poppy, respectively. The enormous structural diversity and biological activities of plant-derived compounds suggest that additional, medicinally relevant compounds remain to be discovered in plants.

While plant natural products continue to be a prime target for drug development, as evidenced by the number of ongoing clinical trials, the clinical potential of these compounds is often curtailed due to low production levels in plant species. For example, use of the blockbuster drug Taxol almost stopped in the early 1990's because the primary source, yew tree bark, could not be used as a sustainable source of the drug. In this particular instance, a Taxol precursor happened to be more readily available in a renewable part of the tree, and a semi-synthetic protocol could be developed to convert it into the drug. While fortuitous, more generalized solutions, such as metabolic engineering of effective plant and microbial production platforms, are urgently needed to ensure that the wealth of bioactive compounds found in plants enter the clinical pipeline and find widespread use in medicine.

High throughput transcriptome sequencing approaches provide a straightforward means for accessing the gene content in organisms with large genomes (i.e. > 100 Mb). Essentially any tissue (independent of genome size and availability of genetic or molecular tools in the organism) can be used to generate cDNAs from mRNA populations and sequenced to generate Expressed Sequence Tags (ESTs) that are assembled into a non-redundant set of sequences (contigs and singleton ESTs) to represent the transcriptome. The transcriptome sequences are then annotated for putative function using a suite of bioinformatic approaches such as sequence searches of protein databases, motif/domain identification, biochemical pathway mapping, and subcellular localization predictions. Transcript abundance data can also be used to provide in-depth expression profiles of individual genes on a per tissue/treatment basis. The deduced function, coupled with expression frequency, can facilitate identification of candidate genes pertinent to the pathway of interest as well as non-

pathway targets (e.g. primary/intermediary metabolism) whose expression is consistent with synthesis of compounds.

Trichrome- The Solanum Trichrome Project: Secretory and glandular trichomes (SGTs) populate the aerial surfaces of approximately 30% of all vascular plant species. These uni- and multi-cellular appendages are proposed to play a critical role in plant protection against various biotic and abiotic stresses including herbivore attack, pathogen infection, extreme temperature, and excessive light. One of the most remarkable features of SGTs is their capacity to synthesize, store, and secrete large amounts of secondary metabolites. Because they are not essential for plant viability, SGTs provide a unique opportunity to study complex and specialized metabolic pathways that operate within the confines of a simple and highly accessible developmental structure. It is noteworthy that many trichome-borne compounds have significant commercial value as pharmaceuticals, fragrances, food additives, and natural pesticides. For this reason, the prospect of exploiting SGTs as “chemical factories” to produce high-value plant products has recently captured the attention of plant biochemists and biotechnologists alike. Realization of this goal will be facilitated by genome-scale research focused on the identification of genes that control the development and biochemical functions of SGTs.

Table 1Hospitals Region CHM COM

McLaren Bay Region (Bay City) Bay City XCommunity Health Center of Branch County

Coldwater X

Beaumont Health System Detroit XBotsford Hospital Detroit XDetroit Medical Center, Osteopathic Division

Detroit X

Detroit Metro Urological Surgical Consortium

Detroit X

DMC Huron Valley- Sinai Hospital Detroit XGarden City Hospital Detroit XHenry Ford Macomb Hospitals Detroit XHenry Ford Wyandotte Hospital Detroit XMcLaren Macomb Detroit XMcLaren Oakland Detroit XMercy Memorial Hospital System Detroit XOakwood Healthcare System Detroit XSt. John Providence Health System- Osteopathic Division

Detroit X

St. Joseph Mercy Oakland Detroit XSt. Mary Mercy Hospital Detroit XGenesys Regional Medical Center Flint X XHamilton Community Health Network Flint XHurley Medical Center Flint XMcLaren- Flint Flint XMetro Health Hospital Grand

RapidsX

Pine Rest Christian Mental Health Services

Grand Rapids

X X

Mercy Health Saint Mary's Grand Rapids

X

Spectrum Grand Rapids

X

Hillsdale Community Health Center Hillsdale XAllegiance Health Jackson XMcLaren- Lansing Lansing XSparrow Healthsystem Lansing X XCovenant Healthcare (Saginaw) Midland XGratiot Medical Center (Alma) Midland XMid Michigan Medical Center- Clare Midland XMid Michigan Medical Center- Gladwin Midland XMid Michigan Medical Center- Midland Midland XSt. Mary's (Saginaw) Midland XMercy Health Hackley Campus- Muskegon

Muskegon X

Mercy Health Muskegon Muskegon XLakeland Healthcare St. Joseph XProMedica Hospital (Toledo) Toledo XAlpena Regional Medical Center Traverse City XCharlevoix Area Hospital Traverse City XKalkaska Memorial Health Center Traverse City XMcLaren Northern Michigan (Petoskey) Traverse City XMercy Hospital Cadillac Traverse City XMercy Hospital Grayling Traverse City XMunson Medical Center Traverse City X XOtsego Memorial Hospital (Gaylord) Traverse City XPaul Oliver Memorial Hospital (Frankfort)

Traverse City X

West Shore Medical Center (Manistee) Traverse City XMarquette General Hospital Upper

PeninsulaX