Access Technology Program Seminars

Volume Electron Microscopy (vEM) is back in the spotlight! Due in large part to Nature recognizing this powerful approach as one of its techniques to watch in 2023, interest in vEM has skyrocketed! Analogous to serial section TEM (ssTEM), vEM constructs large stacks of 2D EM images, which can be aligned and/or segmented to permit greater context to resin embedded cellular and tissue samples at very high resolution. vEM offers a large advantage over ssTEM through automation, FOV, and ease of use, without appreciable compromise. In this session, we will differentiate some of these approaches, compare/contrast the benefits of each, and present example data.

Transmission electron microscopy (TEM) has been an important technology in cell and structural biology ever since it was first used in the early 1940s. The most frequently used TEM application in cell biology entails imaging-stained thin sections of plastic-embedded cells by the passage of an electron beam through the sample such that the beam will be absorbed and scattered, producing contrast and an image. Dr. de Val will present how the current TEM instruments at the Integrated Imaging Advanced Electron Microscopy Facility can be used for Life Sciences applications.

This seminar will describe the services provided by the Nutrition Research Center, including the development of menus, diets, beverages, meal provision, assessment of dietary intake, clinical phenotyping, and food analysis. The seminar will provide examples of research studies already using the services of the Center.

Central laboratory facilities, large-scale biomarker identification studies, and drug discovery campaigns, all rely on high-throughput experimentation, either in terms of organic synthesis or on the analysis of complex biological samples. Traditionally the use of mass spectrometry (MS) in these applications has heavily relied on sample preparation and purification approaches prior to analysis. This, although effective at dealing with complex matrices, drastically limits the inherent throughput of MS analysis and generates multiple challenges when dealing with large-scale sample cohorts. Here we describe the operation and several applications of an automated robotic platform, available now as a Discovery Park Facility, based on desorption electrospray ionization (DESI) MS for the rapid and direct (i.e. no sample workup needed) analysis of high-density (6,144 samples per plate) arrays of samples with throughputs better than 1 sample per second, including relevant examples in biomarker studies, drug functionalization, and bioactivity assessment for drug discovery.

The Oncology Research Information Exchange Network (ORIEN) and its partnering engine, Aster Insights, have developed rich clinical and molecular data resources that are unparalleled by other publicly available or siloed research datasets. While data-sharing is foundational to ORIEN, the network has developed a strong culture of multidisciplinary collaboration between member institutions. This thought-sharing is instrumental in our collective impact as a research network. Attendees will learn about the breadth and depth of the current data available to ORIEN members, how to explore for hypothesis generation, channels of access for publications or grants, new data modalities becoming available, and how to get plugged into a dynamic network of cross-functional researchers in their areas of interest.

Nuclear magnet resonance (NMR) is a powerful technique to detect and characterize 3D structures and dynamics of biomacromolecules and their interactions. It has emerged as an excellent tool for identifying small organic molecules that weakly bind to a target macromolecule and will then be modified or added to another small molecule to act as a potent inhibitor. The Chemical Genomics Core facility is equipped with a 600 MHz solution NMR with cryo-probe for structure elucidation of biomolecules and interaction studies. In this seminar, Dr. Rai will explain how to use NMR as a tool for fragment-based drug discovery and how to utilize this approach to identify and validate initial hits and generate leads.

In vivo rodent behavior studies have been criticized for having poor translation to human disease. This is primarily due to high failure rates in drug discovery research. Reasons could be poor construct, mechanistic or face validity, and inaccurate interpretations of results. The development of rodent behavior cores may help bridge the translational gap by developing new models and by having behavior experts to reduce poor interpretations and ensure validity. Core facilities can also develop standard protocols to be used across institutions and disciplines. Here we will discuss ways to increase the translational value of rodent behavior tasks by discussing the need for standardize protocols and newer tasks, like touchscreen tests that can mimic tests performed by humans and machine learning to identify other behaviors that our current methods are not able to detect.

Engineering conditional alleles in mice has historically posed a challenge. However, in a recent proof-of-concept study, we made significant progress using a novel technology that employs a short artificial intron to create conditional alleles in mice. This innovative method, based on the Cre-loxP system, involves inserting a short DNA segment containing basic intron elements flanked by loxP sites within an exon. Under normal circumstances (without Cre), this DNA segment functions as an intron and is efficiently removed during splicing, allowing normal gene expression. Conversely, in the presence of Cre, the intronic sequences are specifically excised, leaving a short DNA segment within the exon. Consequently, this altered DNA segment evades recognition by the splicing machinery, resulting in gene inactivation. Our findings expand the potential of this approach for engineering conditional alleles in mice, and ongoing investigations aim to evaluate its universality.

Learn more about the services offered by Regenstrief Data Services (RDS). We will also review the data that is available, conditions for use of the data, as well as processes to get data.

Global Online Biomarker Database (GOBIOM) is a repository of validated and putative biomarkers, providing actionable insights into the biomarker-disease relationship. GOBIOM delivers comprehensive pre-clinical and clinical biomarker intelligence integrated from diverse global sources, providing critical insights into diagnosis, prognosis, disease progression, treatment response, efficacy, and toxicity. Information is gathered from >200,000 sources which include clinical trials, literature databases, scientific conferences, regulatory-approved documents, patents, etc. Some of the highlights of the platform include:

• Dedicated modules for Genetic Variants, Pharmacogenomics, Marker Phenotypes, Approved Diagnostics and Drug Labels
• Diverse analytical tools such as Comparative Analysis, Heatmap Analysis, Gene Variant Analysis, Dashboards, and Chromosomal View
• Comprehensive and structured reports focused on Biomarker, Indication or Drug

Cryo-fluorescence tomography (CFT) is whole-animal volumetric imaging with high resolution and sensitivity. In this seminar, you will learn how CFT uniquely enables researchers to overcome the significant challenge of comprehensively documenting drug distribution, protein expression, and other biochemical processes throughout the entire tissue or animal. EMIT Imaging, the leader in CFT instrumentation and services, has developed XerraTM, a state-of-the-art CFT platform currently used by pharmaceutical, biotechnology, and academic researchers across a broad range of application areas in preclinical research, including whole-body drug distribution, screening candidate drugs and delivery systems, whole-body therapeutic protein expression, multiplexed co-localization of drugs with targets, and on-target/off-target tissue identification.

The IU School of Medicine Chemical Genomics Core provides sophisticated small molecule informatics, design, and synthesis, as well as molecule analysis. Dr. Zeng will introduce the medicinal and analytical chemistry capabilities available and show examples of small molecule inhibitor drug discovery and molecule analysis by LC/QTOF and NMR.

The IU School of Medicine Chemical Genomics Core provides sophisticated small molecule informatics, design, and synthesis, as well as molecule analysis. Dr. Zeng will introduce the medicinal and analytical chemistry capabilities available and show examples of small molecule inhibitor drug discovery and molecule analysis by LC/QTOF and NMR.

The Indiana CTSI is involved in two initiatives to support researchers. One is, All IN for Health, an initiative of the Indiana CTSI, to engage the public in bi-directional conversations to improve the public understanding of the role and value of research. This initiative partners with the community to design, talk about, and share health research and its findings to the public in lay terms. The All IN for Health Resources are available to all Indiana CTSI Research Teams. The second, All of Us is a large national research program conducted by NIH to enroll a million, primarily medically underserved, into a biorepository. Currently, there is over 700,000 adult persons enrolled. Researchers can create a workbench to utilize this dataset which contains survey data, EMR data, genomic sequencing, physical measurements, and digital health data. The Indiana CTSI is part of a consortium of CTSAs to assist researchers in utilizing the All of Us data.

This presentation highlights radiopharmaceutical production and development resources available through the IUSM In-Vivo Imaging Core. The PET radiopharmaceuticals currently (or soon to be) available through Core resources and their application to disease management and therapeutic development in cardiology, neuroscience and oncology will be described. These include selective radiopharmaceuticals for non-invasive measurement of multiple metabolic processes (protein synthesis, lipid biosynthesis, oxidative metabolism, glutamine metabolism, blood flow/tissue perfusion), as well as binding to specific receptors and biomarkers. Additionally, opportunities for collaborative research efforts with faculty members in the Molecular Imaging Ligand Development Program (MILDP) of the IUSM Department of Radiology & Imaging Sciences will be presented. Such efforts include development of novel PET radiopharmaceuticals and novel imaging methods using previously reported radiopharmaceuticals not currently available through the Core.

We will review the fundamentals and applications of mass spectrometry imaging (MSI) and share current data generated at the Metabolite Profiling Facility. MSI is a label-free and non-destructive technology to profile hundreds of lipids and metabolites in an untargeted fashion. The application section will focus on the use of desorption electrospray ionization (DESI) ion source coupled to a high mass resolution mass spectrometer (Waters Synapt XS). DESI-MSI allows mapping the location and abundance of small molecules present in tissue sections without the need for sample preparation other than sectioning the tissue and placing it onto regular glass slides. The tissue sections can also be imaged multiple times at the positive and negative ion modes before being processed for histological analysis. Therefore, different experiments can be perfectly overlaid to obtain combined morphological and molecular data.

Research Jam, Indiana CTSI’s Patient Engagement Core, is an interdisciplinary team of healthcare, research, and design professionals using Human-Centered Design methods and best practices in Visual Communication to make research more relevant to the communities that would benefit from it. In this seminar, you will learn about Research Jam’s process for patient engagement and visual communication, and how it may be applicable to your own projects.

The Chemical Genomics Core (CGCF) is using in vitro evolution of phage display of diverse libraries to yield likely interaction with target proteins. Traditional M13 DNA phages with 7-18-mer nanobody libraries are used to map probe candidates binding specific target(s). An attractive alternative system is RNA-coliphage Qβ based on its error-prone replication. Both M13 and Qβ phages are being used separately and in combination as part of the CGCF’s Point-Of-Care tools. Examples of phage display applications include designing mimics of extracellular protein-protein interactions, intracellular protein-binding domains, enzyme inhibitors, new functional peptides (peptides binding RNA/DNA), and drug discovery in pharmaceutical biotechnology. Applications related to antibodies include scFv epitopes, checkpoint inhibitors, nanobodies, and engineering new binding affinity and specificity

As the saying goes, a picture is worth a thousand words. Transmission electron microscopy (TEM) is an important technology in cell and structural biology that creates images of cells by passing an electron beam through the sample. Recent advancements in cryo-EM have enabled imaging of proteins and cellular structures at atomic resolution from purified proteins in vitro as well as in situ as they exist in the cell. This seminar will describe the capabilities of the Glacios cryo-TEM at iCEM and provide an overview of additional new capabilities that are possible with add-on accessory instruments. Examples of recent results and insights obtained from this instrument related to cancer and other diseases will be highlighted.

In this seminar, we will cover the capabilities of the core from simple toxicity testing of existing or novel drugs created in your lab, to efficacy testing of your drug, repurposed drug, or novel therapy in disease or especially cancer research. This will include orthotopic implantation, imaging, intracranial tumor studies, devices used in therapies, PDX models, and use of humanized mice.

The Oncology Research Information Exchange Network (ORIEN) enables researchers to access high-quality cancer clinical and genomic data for their research. There are also opportunities to access biospecimens from targeted patients. Data is generated from consenting patients recruited at one of 18 participating cancer centers spread across the United States, allowing researchers to access a rich data resource, and potentially biospecimens, from a greater number of participants than from one single institution. Attendees will learn how the samples are identified to be a part of the network, what data is available from each one, what types and numbers of samples are available at IUSCCC, how to access the data, and how to submit a proposal for a network-wide project to access data.

This presentation will provide a brief overview of the LAR facilities and the capabilities available for animal research on the IU-Bloomington campus. Participants will learn how the IVIS Lumina X5 non-invasive in vivo bioluminescent/ fluorescent imaging system can be used in their research. A description of the imaging technology, how the system can reduce animal numbers for certain studies, and examples of how the IVIS system has been utilized by researchers for publications and grant preliminary data will be provided.

The Light Microscopy Imaging Center (LMIC) provides user-friendly access to state-of-the-art light microscopy for the IU research community. The LMIC promotes the development of researchers that are knowledgeable, confident, and comfortable in the use of microscopes. The facility’s instrumentation ranges from stereomicroscopes to super-resolution systems and is primarily focused on life-sciences specimens. Available equipment includes primarily inverted platforms for fluorescence imaging including Spinning-Disk confocal, laser-scanning confocal, structured illumination, TIRF, and fluorescence lifetime imaging with modules for FRET and other live-cell methods. The LMIC offers hands-on training for users and after-hours access for trained research personnel. In this seminar, you will learn about the system that is best suited for your experiments, why using confocal instead of wide-field fluorescence is not necessary, and when it becomes the only option. We will also discuss when to utilize super-resolution microscopy or time-resolved lifetime imaging. Additionally, we will explore techniques that provide complementary results and discover how to obtain the best image with more reliable data.

Spatial discoveries happen at many scales – at spatial whole transcriptome to spatial single cell. And, regardless of whether you’re looking to discover new biomarkers, or understand how disease progresses, or building a cell atlas of your tissue, the solutions and team at NanoString are the ones that will get you to your discoveries faster.

WideSeq, a service offered by the Purdue Genomics Core, spans the gap between small Sanger and large Illumina sequencing tasks. This allows, for example, sequencing of an entire plasmid construct at an affordable cost. Any double-stranded DNA template up to around 100 kb can generate useful results. Various use cases will be discussed. Sanger sequencing costs orders of magnitude more per base of sequence generated than Illumina Next Generation sequencing. But the costs of Illumina sequencing are in units of “runs”, rather than individual reads or bases. Even the smallest Illumina run generates vastly more sequence than is useful or cost-effective to deploy against a Sanger-level task. The Purdue Genomics Core gathers samples submitted to it, constructs Illumina libraries from them to be run on a MiSeq once per two weeks. Some informatics, like de novo assembly, are performed and the results returned as a web page

What is the one thing in life that completely affects us on multiple levels? It can affect us not only physiologically, but also mentally. This one thing also has the ability to be beneficial and detrimental. The answer is stress. By decreasing stress in our animal subjects during sampling we can produce higher quality data sets with fewer animals. The Purdue Translational Pharmacology (PTP) facility uses the Culex Automated Sampling System for rodents and swine to minimize pain and distress often caused by traditional sampling methods, which in turn produces quality data for our researchers. On top of reducing stress, the Culex automated sampling system can be used to collect multiple data sets from the same animal allowing you to reduce inter-animal variability in your studies. Please join us in finding out more about what the PTP can offer.

The IU School of Medicine Center for Proteome Analysis (CPA) utilizes state-of-the-art mass spectrometry techniques to quantify and detect changes in protein abundance, post-translation modifications, and stability. Recent projects have included sample types ranging from mouse brain regions, skeletal muscle, serum, subcellular fractionations, and even crickets! This presentation covers some current applications within the CPA.

The Chemical Genomics Core Facility is equipped with various high-throughput technologies to aid PIs in traditional chemical compound screening, plate-based assay development, new arrayed CRISPR screening, and high content analysis using high-throughput microscopic imaging. We serve as a bridge between your concept studies to future drug discovery.

Since the early 1980’s, the Indiana University Center for Survey Research (CSR) has partnered with world-class researchers to plan for, gather, and analyze high-quality data that advance knowledge and humankind. The CSR has conducted thousands of quantitative and qualitative research projects, using surveys, interviews, focus groups, and a wide range of other methods, including collection of medical specimens and environmental samples. In this presentation, we will take you on a journey through our diverse set of services from questionnaire design and survey programming to medical specimen collection and coding of qualitative data. We will also spotlight past collaborations that have used survey science with high real-world impact in improving health and well-being.

The purpose of this presentation is to describe the generation of conditional alleles in mice using the DEgradation based on Cre-regulated Artificial Intron (DECAI) approach. CRISPR-mediated insertion of the short DECAI cassette within exon 3 of Scyl1 and the functionality of the allele are reported. This strategy has the potential to simplify the process of generating mice with conditional alleles

The Preclinical Modeling and Therapeutics Core (PMTC) is a recently consolidated core consisting of the Angio BioCore and the In Vivo Therapeutics Core. The PMTC facilitates the development and testing of pharmacological and cellular therapies for cancer. It provides advanced resources essential for the preclinical validation of novel drug targets and biomarkers of cancer. In this seminar, the team will provide a brief overview of services offered. This will be followed by focused discussions on the Incucyte S3 Live-Cell Analysis (Sartorius) for in vitro cellular response studies and the IVIS SpectrumCT In Vivo Imaging System (PerkinElmer) for in vivo tracking of tumor response.

Proteins are the building blocks of life. During this seminar we will take a closer look at how we can use these molecules for multiple biotechnological applications including diagnostics, therapy, chemical synthesis, etc. The proteins, however, mostly need to be engineered at both protein or gene level to meet the conditions required for industrial applications or for production.For example, some enzymes require that are active at extreme conditions, such as high temperature or very low pH. Low cost is in general a main concern for multiple applications therefore engineering cells and proteins for high production is very important. This seminar will describedifferent problems that we encounter when taking proteins from nature and trying to use them for an industrial application and it will discuss the methods that we are using for making them fit for the biotechnological process.

Mass spectrometry (MS)-based proteomics is routinely applied to address a large range of biological questions, mainly because of its unparalleled ability to acquire high-content quantitative information about biological samples of enormous complexity. The core MS technologies, including the instrumentation and the methods for data acquisition and analysis, have significantly advanced, and will continue to advance in the quest for further improvement in sensitivity, throughput and proteome coverage. In this presentation, I will highlight various proteomics approaches that are currently applied at the Purdue Proteomics Facility, and their impact on understanding cell biology and diseases. Citing specific examples, I will discuss how functional proteomics has been used to learn about the molecular mechanisms of complex biological processes; how to design a successful proteomic experiment tailored to a specific project or biological question; and what additional methods can be integrated to make important biological discoveries. Finally, I will discuss how these lessons or new discoveries might guide future applications.

The Behavioral Phenotyping Core (BPC) is located within the Stark Neurosciences Research Institute at the Indiana University School of Medicine. The BPC has diverse capabilities to evaluate in vivo physiology and behavior of mice and rats. During this seminar you will learn about the automated technology we use to characterize sensory, motor, and autonomic functioning. We have multiple techniques to phenotype affective, motivational, and cognitive domains of behavior that may be altered by genetic, environmental, and pharmacological manipulations. Finally, we will discuss the power of linking behavioral outcomes with your pathology or ‘omics endpoints.

Nuclear Magnetic Resonance (NMR) spectroscopy enables analysis of natural products, metabolites, synthetic drug candidates, peptides, and proteins to determine their purity, structures, and interactions. Compounds in complex mixtures may be identified based on diffusion coefficients as well as by directly fitting the component spectra. Binding interactions are sensitively detected and mapped on the molecular structures while binding kinetics are accessible from NMR line shapes in titration experiments. This seminar will highlight the most NMR prominent capabilities relevant to biomedical research and drug design available to CTSI researchers at the Magnetic Resonance Research Center at the University of Notre Dame.

The Biospecimen Collection and Banking Core has been created to house four separate biospecimen collection entities which were part of the IU Simon Comprehensive Cancer Center. This talk will share which facilities are included and what services the Core will offer. Bring any questions you might have on the collection, processing and use of biospecimens in your research.

Single-cell RNA (scRNA) analysis technologies have emerged as powerful tools for in-depth analysis of cellular heterogeneity of different cell types and rare populations. Cell sorting is an indispensable tool used within the single-cell transcriptomics workflow. It delivers highly pure and viable target cells and nuclei for sequencing reactions resulting in an overall improvement of the results. In this talk, we will discuss how the Sony Cell Sorters have been used in this workflow and why the use of microfluidics chip provides a plug-and-play solution to users, enabling a streamlined approach in this application. Best practices used for sorting different cells, tissues and nuclei will also be discussed.

Dive deeper into disease pathology with 10x Genomics Visium Spatial Products, which allow you to understand your tissue sample like never before by profiling spatial gene expression alongside histological analysis of H&E stained sections to examine tissue anatomy or immunofluorescence for protein detection. Map the whole transcriptome with morphological context or focus on your genes of interest using targeted gene expression panels—choose from pre-designed panels or design your own—to make novel discoveries in normal development, disease pathology, and clinical translational research.

During this seminar you will learn about the benefits of MicroScale Thermophoresis (MST), an immobilization-free tool for quantitative analysis of molecular interactions using minimal sample volume. MST measures a broad range of binding affinities for many types of interactions by detecting changes in fluorescence intensity while a temperature gradient is applied over time. Different interaction measurements will be discussed that are possible with the Monolith NT instruments currently available at the Chemical Genomics Facility at Purdue Institute for Drug Discovery. Bring your questions for deciding on the best conditions to measure your interactions of interest.

The CODEX system facilitates multiplexed imaging of 50+ probes within thin-sectioned tissue by utilizing a panel of antibodies conjugated to unique DNA barcodes. The tissue sample is incubated with the full panel of antibody-DNA conjugates, which are then labeled with fluorescent probes and imaged three at a time. The fluorescent probes are then stripped, and another set of three fluorescent probes are added, imaged and stripped. The process is repeated for multiple cycles, giving you a highly multiplexed image of entire millimeter-scale samples. A member of the Indiana Center for Biological Microscopy, Dr. Connor Gulbronson will be discussing the technique, describing improvements that he’s made to the CODEX system and demonstrating the new HALO image analysis software available in the core facility.

In this seminar we will present a method for the exploratory analysis of lipids named multiple reaction monitoring (MRM)-profiling. The method employs a different analytical strategy compared to untargeted lipidomics by LC-MS. First, there is no liquid chromatography; the lipid extracts are injected directly into the source of the mass spectrometer, which confers speed to the analyses. We then trust the mass spectrometer to do the separation of the ions “internally” by using scan types that can profile chemical functionalities, and specific combinations of parent (intact) and fragment ions related to specific lipid classes. The parent-fragment ion scan is known as the MRM scan, and it is the most sensitive scan type in mass spectrometry. The MRM scan data on lipids is analyzed as a chemical profile, hence,the name MRM-profiling. We will also discuss the lipidomics capabilities, including LC-MS, available at the Metabolite Profiling Facility at Bindley Bioscience Center at Purdue University.

Light-sheet fluorescence microscopy (LSFM) enables large-scale, three-dimensional imaging at high imaging speeds with less phototoxicity and photobleaching. The Bruker MuVi microscope provides flexible illumination and detection configurations suitable for imaging samples from fields as diverse as cell and developmental biology, neuroscience, oncology, and plant research. In this presentation, you can expect to learn the advantages of light-sheet fluorescence microscopy and how this technique can be adapted to image a variety of live, fixed or cleared samples.

In this webinar we will discuss popular applications that utilize home-brew library preps with Illumina Sequencing as a downstream readout. This will include an overview of epigenetic methods designed to look at regions of open chromatin (ATAC-Seq), binding sites of DNA-associated proteins (ChIP-Seq/Cut and Run), and detection of long-range DNA interactions (Hi-C). Additionally, we will look at how Illumina Sequencing can be used as an effective strategy in genome wide CRISPR screens for quantification of sgRNAs as well as methods that allow the detection of transcriptional changes observed in the enriched or depletion knockout populations.

The Bruker 9.4T magnetic resonance (MR) scanner delivers in-vivo/ex-vivo images with high spatial and temporal resolution. Parallel with any MRI method on this machine, the compatible PET insert offers high resolution, high sensitivity, and high quantification accuracy, allowing for simultaneous PET/MR imaging in basic research and translational medicine. Applications in multiple fields are available with these advanced preclinical imaging solutions, including, but not limited to: oncology, neurology, cardiology, inflammation, functional and anatomical neuroimaging, orthopedics, cardiac imaging, and stroke models.