Before the launch of the Center for Cell Signaling in Gastroenterology (C-SiG), digestive disease research at Mayo Clinic was often organized by organ or disease, reinforcing a silo-like approach to scientific collaborations. Realizing the limitations of this approach, the center leadership reorganized investigators into three highly focused, dynamic, interactive research themes focused on mechanisms of cellular and molecular processes, as opposed to specific organ physiology and cell types. The current themes are:

Intracellular Signaling, including:

• Receptors
• Ion channels
• Ciliary signaling
• Intracellular messengers
• Autophagy
• Metabolism

Cell-to-Cell Communication, including:

• Extracellular vesicles
• iPS cells
• Organoids
• Microbiome
• Cell trafficking and migration
• Cytokines and inflammation

Genetics & Epigenetics, including:

• Gene transcription, splicing & editing
• MicroRNAs
• Chromatin dynamics

In addition to the research themes, the faculty in the Center for Cell Signaling in Gastroenterology are also organized into three disease focus areas of long-standing strength at Mayo Clinic:

Enteric neurosciences and motility, including:

• Fecal incontinence
• Irritable bowel syndrome
• Gastroparesis
• Functional gastrointestinal disorders

Liver pathobiology, including:

• Nonalcoholic steatohepatitis
• Primary sclerosing cholangitis
• Polycystic liver disease
• Primary biliary cirrhosis
• Biliary cryptosporidiosis
• Alcohol-based liver disease

Inflammation and cell transformation, including:

• Barrett’s esophagus
• Colorectal cancer
• Pancreatic cancer
• Inflammatory bowel disease
• Hepatocellular carcinoma
• Crohn’s disease
• Ulcerative colitis
• Celiac disease
• Cholangiocarcinoma

While the emphasis of the Mayo Clinic Center for Cell Signaling in Gastroenterology is on supporting the research themes, the disease focus areas set the stage for translating basic science discoveries to human disease by providing structure and the opportunity for additional collaboration and synergy. The disease focus areas provide a forum for basic scientists and clinicians to exchange information and form collaborative alliances. These relationships are beneficial to basic scientists, who need tissues from rare disease states and need the help of clinicians to identify potential patients. The clinicians, in turn, benefit from collaboration with basic scientists who can perform pilot studies of research ideas generated from patient care.

Cores
Shared resources (cores) foster productivity, synergy and new research ideas and techniques in an efficient, cost-effective manner. The Mayo Clinic Center for Cell Signaling in Gastroenterology offers specialized equipment, technologies, methodologies, reagents and expertise to assist its faculty members and their research teams through three cores:

• Clinical Core: Provides centralized access for normal and abnormal gastrointestinal biospecimen acquisition and processing
• Gene Editing and Cell Engineering Core: Provides plasmids, transposons, TALENs and CRISPRs that can be applied to mammalian and nonmammalian model development
• Optical Microscopy Core: Provides consultative expertise and training for sophisticated cell imaging technologies and applications

Clinical Core
The Clinical Core of the Mayo Clinic Center for Cell Signaling in Gastroenterology supports faculty research by facilitating access to human biospecimens through two primary objectives:

• Centralizing, expediting and facilitating access to digestive disease-related biospecimens
• Enhancing digestive disease-related biospecimen repositories within Mayo Clinic

Director
The director of the Clinical Core is Lisa A. Boardman, M.D.

Services
The Clinical Core offers several services, primarily to Mayo Clinic Center for Cell Signaling in Gastroenterology faculty and their laboratory team members, including:

• Centralized access to 18 participating Mayo Clinic GI biobanks and other institutional biospecimen resources
• Institutional Review Board (IRB) protocol development and modification
• Identification of biospecimens meeting specific research criteria
• Pathologist review of tissues
• Biospecimen processing request form coordination
• De-identified, phenotypic and demographic data
• Standardized epidemiological questionnaires for GI biobanks
• Coordination of fresh tissue acquisition from surgical pathology
• Fecal collection kits and storage for microbiome-related projects
• Inventory management software deployment and customization

Access
Research teams from NIDDK-funded Digestive Disease Research Core Centers outside of Mayo Clinic may access select core services as resources permit by emailing requests to rstcsig@mayo.edu.

Gene Editing and Cell Engineering Core
The Gene Editing and Cell Engineering Core of the Mayo Clinic Center for Cell Signaling in Gastroenterology is a central repository for gene editing expertise and supports faculty research through three primary objectives:

• Accelerating research by connecting and educating faculty about gene editing and cell engineering
• Delivering new gene editing and cell engineering tools and technologies that are needed by faculty
• Establishing cutting-edge genetic tools for genome editing, including zinc finger nucleases (ZFNs), TALENs, Cas9 Custom Restriction Enzyme Systems (CRISPRs) and locus-specific genome editing tools that can be applied to model systems development, including cell lines, organoids, zebrafish, rats, mice and drosophila.

Director
The director of the Gene Editing and Cell Engineering Core is Stephen C. Ekker, Ph.D.

Services
The Gene Editing and Cell Engineering Core offers a variety of services, primarily to Mayo Clinic Center for Cell Signaling in Gastroenterology faculty and their laboratory members, including:

• Designing, constructing and validating custom plasmids and other DNA vectors.
• Making custom genome engineering reagents, including TALENs, transposons, bacterial artificial chromosomes and CRISPRs.
• Providing consults and training on a variety of topics, including rodent and zebrafish transgenic and knockout model development support; viral delivery of siRNA; transposons for somatic genetic engineering; and in vivo imaging.

Access
Researchers outside of Mayo Clinic may access Gene Editing and Cell Engineering Core TALEN services or training by emailing requests to rstcsig@mayo.edu.

Optical Microscopy Core

The Optical Microscopy Core of the Center for Mayo Clinic Center for Cell Signaling in Gastroenterology provides essential optical technologies and applications expertise to support faculty research through three primary objectives:

• Providing reliable, accessible and state-of-the-art microscopic technology to all faculty members that facilitates their study of GI cellular signaling cascades
• Educating and training faculty members in the use of both basic and sophisticated cellular imaging methods
• Developing and applying state-of-the-art optical imaging technologies to GI tissues and cells based on faculty needs

Director
The director of the Optical Microscopy Core is Mark A. McNiven, Ph.D.

Services
The Optical Microscopy Core offers a variety of services, primarily to the Mayo Clinic Center for Cell Signaling in Gastroenterology faculty and their laboratory members, such as consults and training on a variety of topics, including:

• High-resolution, real-time imaging of live cells
• Confocal microscopy
• Confocal microscopy coupled with computer-based 3-D image reconstruction
• Fluorescence resonance energy transfer (FRET)
• Fluorescence recovery after photobleaching (FRAP)
• Expression and use of fluorescence-based bioprobes
• Cellular microinjection
• Total internal reflection fluorescence (TIRF)
• Cell and tissue computer morphometry
• Imaging cells in 3-D matrix
• Data interpretation
• Gel degradation assay
• Histology microscopy
• 2-photon microscopy
• Super-resolution microscopy

Access
Research teams from NIDDK-funded Digestive Diseases Research Core Centers outside of Mayo Clinic may access select core services as resources permit by emailing requests to rstcsig@mayo.edu.

Center for Cell Signaling in Gastroenterology (C-SiG)
Mayo Clinic
Mayo Building, 9th Floor
200 First St. SW
Rochester, MN 55905
Email: rstcsig@mayo.edu

Development inquiries:
Department of Development
Mayo Clinic
200 First St. SW
Rochester, MN 55905
Phone: 507-284-8540 or 800-297-1185 (toll-free)

http://www.mayo.edu/research/centers-programs/center-cell-signaling-gastroenterology-c-sig