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Department of Systems Biology Opens New Biotechnology Development Hub

Peter Sims, Sagi Shapira, and Harris Wang

Assistant Professors Peter Sims, Sagi Shapira, and Harris Wang recently moved into a new Department of Systems Biology laboratory space designed to facilitate the development of new technologies for biological and biomedical research. Photo: Lynn Saville.

The Columbia University Department of Systems Biology has opened a new experimental research hub focused on biotechnology development. Occupying one and a half floors in the Mary Woodard Lasker Biomedical Research Building at Columbia University Medical Center, the facility will promote the design and implementation of new experimental methods for the study and engineering of biological systems. It will also enable a substantial expansion of Columbia’s next-generation genome sequencing capabilities.

The first occupants of the new facility are the laboratories of Department of Systems Biology Assistant Professors Sagi Shapira, Peter Sims, and Harris Wang, along with the Genome Sequencing and Analysis Center of the JP Sulzberger Columbia Genome Center. The community is slated to grow, as currently unoccupied space will soon accommodate additional Columbia University faculty labs that are also developing new biotechnologies.

“Technology drives science,” says Department of Systems Biology Chair Andrea Califano, “and the ability to design new technologies can make it possible to answer questions that no one else can. By bringing technology-focused investigators and the Genome Center’s sequencing infrastructure together in the same physical location, our goal is that the new Lasker facility will give the Department of Systems Biology — and the entire Columbia University research community — access to unique applications for biological and biomedical research.” 

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Hynek Wichterle Appointed to Columbia Genome Center

Hynek WichterleThe JP Sulzberger Columbia Genome Center is pleased to announce that Hynek Wichterle has been appointed as associate director. In this role he will advise on stem cell related projects and coordinate interactions between Columbia Stem Cell Facility and the Columbia Genome Center's High-Throughput Screening Facility.

In addition to his position at the Columbia Genome Center, Dr. Wichterle is also an associate professor holding a joint appointment in the Departments of Pathology & Cell Biology and Neuroscience (in Neurology) at Columbia University Medical Center. He received his MS degree from Charles University in Prague and his PhD degree from The Rockefeller University. He trained at Columbia University, where he became assistant professor in 2004 and associate professor in 2012. He serves as a co-director of the Columbia Stem Cell Initiative and as a Vice-Chief of the Division of Regenerative Medicine in the Department of Rehabilitation & Regenerative Medicine.

Dr. Wichterle developed groundbreaking methods for producing spinal cord neurons from pluripotent embryonic stem cells in a culture dish. The process faithfully recapitulates normal embryonic development, providing a unique opportunity to study and experimentally probe nerve cells in a controlled environment outside of the embryo. He is using the system to decode transcriptional programs that control genes important for neuronal differentiation and function. His lab also capitalizes on the unlimited source of spinal neurons to study motor neuron degenerative diseases, such as amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease), with the goal of discovering new drugs for these currently untreatable, devastating conditions.

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Improving Single-Cell RNA-Seq at the Columbia Genome Center

Fluidigm C1 Single-Cell Plate

At the core of the Fluidigm C1 Single-Cell Auto Prep System is a 96-well plate containing microfluidics. After individual cells are isolated in their own wells, the device amplifies their cDNA for genome-wide gene expression profiling. Scientists at the Columbia Genome Center are developing methods for addressing the technical and analytical challenges of single-cell RNA sequencing, and have begun generating some exciting data.

Since the invention of the first microscope, a procession of new technologies has enabled scientists to study individual cells at increasingly fine levels of detail. The last two years have witnessed an important next stage in this evolution, with the arrival of the first devices for genetically profiling single cells on a genome-wide scale.

The first commercial product in this field is the Fluidigm C1 Single-Cell Auto Prep System, which uses microfluidics to isolate single cells and offers the ability to generate gene expression profiles for up to 96 cells at a time. But because of the novelty of the technology and the inherent difficulties of working with single cells, it has presented a number of technical challenges for researchers interested in exploring biology at this level.

Now, scientists at the JP Sulzberger Columbia Genome Center led by Assistant Professors Peter Sims and Yufeng Shen have developed an experimental and computational pipeline that optimizes the C1’s capabilities. And even as they work to solve some of the challenges that are inherent to single-cell research, their approach has begun generating some exciting data for studying genetics in a variety of cell types.

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Columbia Launches Initiative to Advance Personalized Medicine

Personalized Medicine

Illustration by Davide Bonazzi, courtesy of Columbia Medicine.

The cover article of the Spring 2014 issue of Columbia Medicine reports on a new, Columbia University-wide effort to harness the potential of new scientific approaches and technological developments to advance the personalized treatment of cancer and other diseases. Announced in February by Columbia President Lee Bollinger, an interdisciplinary task force has been formed to coordinate the scientific, policy, and clinical components necessary to achieve this goal. The Department of Systems Biology, including its Center for Computational Biology and Bioinformatics and JP Sulzberger Columbia Genome Center, has been identified as a key partner in this interdisciplinary effort. As the article reports:

Rapidly evolving technologies that make DNA sequencing dramatically faster and less expensive along with new technologies to monitor virtually all aspects of cell physiology have led to the generation of unprecedented amounts of information (big data) that is starting to yield to new computational approaches and high speed computers, all of which promise to make diagnosis and treatment as patient-specific and precise as possible.

To harness the potential created by these scientific advances for the benefit of patients, [College of Physicians & Surgeons] Dean Lee Goldman, MD, has made personalized medicine a key goal of the medical school’s strategic plan. “At Columbia, we have enthusiastic consensus in support of personalized medicine—the personalized application of scientific advances to modern diagnosis and treatment, easily accessible and attentive care for the people who entrust us with their health, and personalized education for each of our individual students,” says Dr. Goldman…

At the center of Columbia’s personalized medicine effort is the new Department of Systems Biology, which brings together researchers specializing in molecular biology, genetics, computational biology and bioinformatics, structural biology, mathematics, chemistry and chemical biology, physics, computer science, and other fields. According to founding director and chair Andrea Califano, PhD, the Clyde and Helen Wu Professor of Chemical Systems Biology, the new department seeks to provide an in-depth, systemwide characterization of all molecular interactions. It is this systems-level approach to disease biology that can systematically identify disease drivers and druggable targets for the 90 percent of cancer patients who lack a clearly actionable genetic mutation. This has become possible only in recent years through major advances in science and technology that require a fully interdisciplinary approach.

The article describes how research by Department of Systems Biology faculty members including Dr. Califano, Nicholas Tatonetti, Brent Stockwell, and Tuuli Lappalainen, along with that of investigators in departments across the university, is contributing to this ambitious initiative. Read the complete article here.

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Columbia Genome Center Now Offers Illumina NextSeq 500 Self-Service

Illumina NextSeq 500 at Columbia University

As genome sequencing technologies evolve, the JP Sulzberger Columbia Genome Center continues to provide the Columbia University biological and biomedical research community access to state-of-the-art tools. In its most recent acquisition, the Genome Center has just installed two Illumina NextSeq 500 sequencers. The NextSeq 500 is a flexible and efficient desktop sequencer that offers powerful high-throughput sequencing capabilities.

Columbia investigators who are experienced with the Illumina next-generation sequencing platform can now schedule time to use the NextSeq 500 for their own research. 

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Peter Sims Appointed to Columbia Genome Center

Peter SimsPeter Sims, an assistant professor in the Columbia University Department of Systems Biology, has been named Associate Director for Novel Technologies at the JP Sulzberger Columbia Genome Center. In this role he will devise, direct, and implement strategies for incorporating new high-throughput experimental methods into the research done at the Genome Center.

Trained as a physical chemist, Dr. Sims has been developing a number of innovative technologies for studying single cells in a high-throughput setting. Using a type of microfluidics called soft lithography, his laboratory has designed a method for creating arrays composed of wells just tens of microns in diameter, small enough to isolate and perform high-throughput experiments on individual cells.  

Appointing Dr. Sims to his new role will enable the Columbia Genome Center to develop a variety of new applications that will benefit researchers across the Columbia University community. 

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Imaging Synapses Using Fluorescent Small Molecule Probes

Imaging synapses

In a test of the Columbia Genome Center's high-content microscopy system, computational image analysis confirmed a high degree of colocalization of green fluorescent protein-labeled synapsin and the dye FM4-64. The researchers plan a high-throughput screen to identify fluroescent small molecules capable of targeting synapses.

Synapses mediate communication between neurons in the brain, making them critical components for neurological activity. Research has shown that synaptic loss and dysfunction play roles in a number of debilitating brain disorders — including Alzheimer’s disease, major depressive disorder, and autism — but currently no effective method exists for identifying and imaging individual synapses in living human brains. Being able to locate and quantify synapses in patients could greatly improve the diagnosis and monitoring of disease, and potentially offer new approaches for treatment.

Clarissa Waites, an assistant professor of pathology and cell biology at the Columbia University College of Physicians & Surgeons, and Dalibor Sames in the Columbia University Department of Chemistry, have recently embarked on a collaboration with the Columbia Genome Center High-Throughput Screening Facility with the goal of identifying small fluorescent molecules that can selectively localize to synapses. If successful, this project could for the first time provide a method for targeting and imaging synapses in the living human brain.

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Columbia Genome Center Holds High-Throughput Screening and Chemistry Symposium

High-throughput screening’s ability to perform thousands of experiments efficiently and under carefully controlled conditions has made it an important tool for basic and translational biological research. At Columbia University, the JP Sulzberger Columbia Genome Center and the Chemical Probe Synthesis Facility provide a flexible platform for researchers interested in applying high-throughput experimentation in their work. On December 17, 2012, the Genome Center hosted a symposium to spotlight its capabilities in high-throughput screening, to explain the important role that synthetic chemistry plays in high-throughput screening, and to describe some recent research projects at Columbia that have utilized these tools.

As High-Throughput Screening Core Scientific Director Charles Karan explained, the Genome Center operates a suite of advanced technologies for automated liquid handling, robotic assay implementation, and high-throughput, high-content microscopy. The Genome Center also offers Columbia University researchers access to several large collections for conducting high-throughput screens. These include the Columbia Cell Line Encyclopedia, which includes 850 cancer cell lines collected from around the world, as well as a chemical diversity library curated by researchers in the Chemical Probe Synthesis Facility. This “tool chest” gives Columbia investigators access to a pre-selected set of compounds that have been predicted to result in the highest quality potential hits. Karan also reported that the Genome Center recently negotiated an arrangement with Sigma Aldrich to give access to the company’s shRNA clones to researchers at Columbia at greatly discounted rates.

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