This Research Rising project will integrate cutting-edge biotechnologies that collect large amounts of data in order to create a more holistic understanding of human diseases and empower the discovery of new drugs to treat them. The principal investigator is Michael Wolfe, Mathias P. Mertes Professor of Medicinal Chemistry. He is joined by faculty colleagues in molecular biosciences, pharmacy, chemistry, electrical engineering & computer science and several departments at KU Medical Center.
Making KU competitive in using big data for drug discovery will require adding faculty with proven expertise and experience in this broad area. We plan to search for four new faculty members whose research involves the use of large datasets for drug discovery, in different but interrelated areas. Specifically, we seek to identify and hire such an investigator for each of four areas: (1) pharmacology, (2) molecular cell biology, (3) chemical biology, and (4) medicinal chemistry. Bringing in investigators into these four areas as it relates to use of big data is expected to lead to synergy as well as providing a hub of expertise for broader collaborations at KU and KUMC.
The Center for Systems Pharmacology & Translational Science (CSPTS) will fund small pilot project grants to support KU investigators with innovative ideas for using big data for drug discovery. This seed funding is to encourage research faculty to think creatively about how their current research can be accelerated, enhanced or expanded by systems-based approaches. Funding will support 5 one-year pilot projects at $50,000 each (one pilot project per year for five years).
Critical to identifying small molecules as tool compounds and therapeutic prototypes is the ability to conduct high-throughput phenotypic screening. This is critical for identifying compounds that perturb a biological process for which the target(s) is not known. Moreover, such screening is critical when the goal is to perturb whole networks, not just a single enzyme or pathway. Although KU's High Throughput Screening Laboratory can conduct some cell-based screening, it is not equipped to conduct phenotypic screening in a high throughput format. Phenotypic HTS approaches are based on utilization of whole cells in two- or three-dimensional growth formats that have potential to faithfully recapitulate human biology.
To fill this gap, the project will purchase a Cytation 10 confocal imaging reader that uses custom confocal and wide-field microscopy in one system. The instrument will be purchased in the first year of the project and set up in the High Throughput Screening Lab, making the facility fully capable of conducting phenotypic high throughput screening with center investigators, pilot project recipients and other campus users.
The Center for Systems Pharmacology & Translational Science will fund, organize and host on campus an annual half-day symposium on systems-based approaches to drug discovery. The symposium will be open to students, staff and faculty in the region and state. An outside speaker will be invited to give a keynote lecture as part of the symposium.
The center will also conduct an annual workshop on systems-based approaches to biology, disease and translational science. In addition, the center will provide travel awards to graduate students and postdoctoral fellows to attend and/or present at scientific conferences related to center-sponsored project.
P. Scott Hefty
Devin C. Koestler
Susan M. Lunte
Nancy A. Muma
Michael S. Wolfe