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.” 

After identifying T cell clones that react against donated kidney tissue in vitro, new computational methods developed in Yufeng Shen's Lab are used to track their frequency following organ transplant. The findings can help to predict transplant rejection or tolerance.

When a patient receives a kidney transplant, a battle often ensues. In many cases, the recipient’s immune system identifies the transplanted kidney as a foreign invader and mounts an aggressive T cell response to eliminate it, leading to a variety of destructive side effects. To minimize complications, many transplant recipients receive drugs that suppress the immune response. These have their own consequences, however, as they can lead to increased risk of infections. For these reasons, scientists have been working to gain a better understanding of the biological mechanisms that determine transplant tolerance and rejection. This knowledge could potentially improve physicians’ ability to predict the viability of an organ transplant and to provide the best approach to immunosuppression therapy based on individual patients’ immune system profiles.

Yufeng Shen, an assistant professor in the Columbia University Department of Systems Biology and JP Sulzberger Columbia Genome Center, together with Megan Sykes, director of the Columbia Center for Translational Immunology at the Columbia University College of Physicians and Surgeons, recently took an encouraging step toward this goal. In a paper published in Science Translational Medicine, they report that the deletion of specific donor-resistant T cell clones in the transplant recipient can support tolerance of a new kidney. Critical to this discovery was the development of a new computational genomics approach by the Shen Lab, which makes it possible to track how frequently rare T cell clones develop and how their frequencies change following transplantation. The paper suggests both a general strategy for understanding the causes of transplant rejection and a means of identifying biomarkers for predicting how well a transplant recipient will tolerate a new kidney.

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.

Peter 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.