Jocelyn Sunseri Selected as Recipient of 2018 Phase-I MolSSI Software Fellowship

Congratulations to Jocelyn Sunseri who was selected as one of only 11 recipients of the 2018 Phase-I MolSSI Software Fellowship. She will receive six months of support in this program funded by the National Science Foundation through Virginia Tech. Jocelyn’s adviser is Dr. David Koes.

For more information, please click here.

Raghav Partha and the Clark and Chikina labs publish in eLife

Subterranean mammals show convergent regression in ocular genes and enhancers, along with adaptation to tunneling

Raghavendran Partha, Bharesh K Chauhan, Zelia Ferreira, Joseph D Robinson, Kira Lathrop, Ken K Nischal, Maria Chikina (corresponding author), Nathan L Clark (corresponding author)

Abstract: The underground environment imposes unique demands on life that have led subterranean species to evolve specialized traits, many of which evolved convergently. We studied convergence in evolutionary rate in subterranean mammals in order to associate phenotypic evolution with specific genetic regions. We identified a strong excess of vision- and skin-related genes that changed at accelerated rates in the subterranean environment due to relaxed constraint and adaptive evolution. We also demonstrate that ocular-specific transcriptional enhancers were convergently accelerated, whereas enhancers active outside the eye were not. Furthermore, several uncharacterized genes and regulatory sequences demonstrated convergence and thus constitute novel candidate sequences for congenital ocular disorders. The strong evidence of convergence in these species indicates that evolution in this environment is recurrent and predictable and can be used to gain insights into phenotype–genotype relationships.

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Dr. Robin Lee Lab publish in Cell Systems

Lee Lab publish in Cell Systems

 

Cell Systems

NF-𝛋B Dynamics Discriminate between TNF Doses in Single Cells

Zhang Q1, Gupta S1, Schipper DL, Kowalczyk GJ, Mancini AE, Faeder JR, Lee REC*

Using an information theory framework and single-cell data, Zhang et al. set out to distinguish between different mechanisms for activation of intracellular signals. They show that heterogeneity between cellular states can lead to underestimates in the capabilities of single cells. In contrast with a switch-like model for pathway activation, they find that single cells can encode multiple levels of response that increase with stimulation strength.

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Dr. Robin E. C. Lee Gives Senior Vice Chancellor’s Research Seminar

Robin E. C. Lee, PhD, assistant professor of computational and systems biology, School of Medicine, delivered the lecture in the 2017 Senior Vice Chancellor’s Research Seminar series on Friday, October 6, from noon–1 p.m. in Lecture Room 6, Scaife Hall* [Add to Calendar]. The title of Lee’s presentation was “Uncovering the Role for ‘Dynamics’ in Mediating Cell-Fate Decisions.” This seminar series was open to all interested University of Pittsburgh and Carnegie Mellon University faculty, students, and staff. Arthur S. Levine, MD, senior vice chancellor for the health sciences and John and Gertrude Petersen Dean of Medicine, introduced Lee and lead the discussion following his lecture.

*Unable to make it to Scaife Hall? *Unable to make it to Scaife Hall?
Dr. Lee’s lecture was available via live stream to people with Pitt login credentials by clicking this link (sign in using your Pitt username and password): https://pitt.hosted.panopto.com/Panopto/Pages/Viewer.aspx?id=f101065c-830d-47e7-a2e5-45a2e9c1ee65.

If you have problems with the video, contact the CSSD help line at 412-624-4357 (4-HELP).


Topic Overview:

In the long-term, Lee’s goal is to understand how single cells process cues from their environment to make irreversible decisions such as whether to proliferate, differentiate, or die. Cell-fate decisions are often influenced by inflammatory factors in the cellular milieu that initiate dynamic reorganization of proteins within the cell. For example, clusters of ligand-bound receptors can transiently recruit cytoplasmic proteins to large complexes near the plasma membrane, whereas other proteins translocate between cellular compartments such as the cytoplasm and the nucleus. It is an emerging principle that dynamic properties of signaling molecules provide temporal codes (i.e., rates of change, or signal amplitude, duration, or frequency, among others) that regulate each cell’s response to a stimulus. Given that there is substantial cell-to-cell heterogeneity, even in a clonal cell line, dynamic mechanisms of signal transduction are generally obscured in fixed-point measurements or averages from a cell population.

In this talk, Lee will discuss his progress in establishing single-cell techniques to study dynamic properties of signal transduction that govern the NF-κB transcriptional system. He will present his and colleagues’ advances using CRISPR-mediated genome editing to generate fluorescent-protein fusions expressed from their endogenous locus in human cells. Lee will also discuss the combination of live-cell imaging, microfluidics, and computational techniques to understand how dynamic properties of molecules within the NF-κB system encode and decode information in single cells. By uncovering the role for “dynamics” in mediating cell-fate decisions, their approaches may eventually lead to the rational design of therapies that target “dynamics” to affect disease.

Taylor Appointed to Distinguished Professor

Congratulations to Dr. D. Lansing Taylor for his appointment to Distinguished Professor.

Dr. Taylor has been with the department since his return to academia in 2010. Prior to that, he held academic appointments at Harvard University and Carnegie Mellon University.

During his time as CMU, he and Dr. Alan Waggoner co-found Biological Detection Systems (BDS) to commercialize the multi-color cyanine dyes and research imaging platform. The company was later acquired by Amersham (now GE Life Sciences). He left CMU in 1997 to found Cellomics, Inc., which developed High Content Screening and later became a part of ThermoFisher Scientific. He then moved on to found Cellumen, which developed a predictive safety assessment platform using primary hepatocytes, multiplexed panels of reagents, reference safety databases and computational biology. He was CEO of Cellumen from 2004 until 2010 when it became part of Cyprotex, a British CRO. He also co-found Cernostics, Inc., a fluorescence-based, tissue systems pathology company that has created a test for selecting at risk Barrett’s esophagus patients.

Dr. Taylor holds >25 U.S. patents, including six focused on cell-based imaging.

His current research links large-scale cell, tissue and human, biomimetic, tissue-engineered model profiling with computational and systems biology to optimize drug discovery and diagnostics based on quantitative systems pharmacology. He is also developing computational tools to identify and quantify heterogeneity.

To further promote Quantitative Systems Pharmacology in the region, he recently created the Pittsburgh Revolution Fund with the goal of bringing the recent advances at Pitt (in collaboration with UPMC, CMU, and UPCI) to the attention of the broader community.

Dr. Taylor has contributed greatly to our department, the Drug Discovery Institute, the University, and to science as a whole. He is well deserved of the distinguished title, and we congratulate him!