CPCB student Jingyu Zhang from the Xing lab published a first-authored paper in NPJ Systems Biology and Applications

The Xing lab publishes a research paper in NPJ Systems Biology and Applications. The article title is Pathway crosstalk enables cells to interpret TGF-β duration, in which the researchers used systems biology approaches to address an intriguing question how a cell reads quantitative information of a signal.

Graduate student Jingyu Zhang and former postdoc researcher Xiaojun Tian (currently assistant professor at Arizona State University) are leading authors. The research was a collaboration between the Xing lab and Dr Simon Watkins at Center for Biological Imaging.

Click here to view the full publication.

2018 CPCB Recruitment Results

The results of our 2018 recruitment process for the CPCB PhD program are in, and we would like to congratulate all of the students who will be joining us this year!

CMU | Pitt

Stefan Andjelkovac
B.S. University of Belgrade
M.S., University of Cambridge

Ali Balci
B.S., Istanbul Technical University
M.S. Koc University

Neha Cheemalavagu
B.S., Case Western Reserve University

Pinar Demetci
B.S., Franklin W. Olin College of Engineering

Mohsen Ferdosi
B.S., Sharif University of Technology

Carly Houghton
B.S., George Washington University
M.A., Johns Hopkins University

Minxue Jia
B.S., Worcester Polytechnic Institute
M.S.E. Johns Hopkins University, Pitt admit

Hyun Woong (Ben) Kim
B.S., Korea Advanced Institute of Science and technology

Yang Ping (Y.P.) Kuo
B.S., University of Washington, Pitt admit

Dongshunyi (Dora) Li
B.S., Hong Kong Univ. of Science and Tech.
M.S. Duke Univ.

Ruogu Lin
B.E., Tsinghua University

Tyler Lovelace
B.S., Texas A&M University, Pitt admit

Sejoon Oh
B.S., Seoul National University

Akash Parvatikar
B.E., M R.V. College of Eng., India
M.S., Univ. of Pittsburgh, Pitt admit

Yutong Qiu
B.S., University of California, San Diego

Elysia Saputra
B.ENG., National University of Singapore, Pitt admit

Yiheng Shen
B.S., Peking University

Haotian Teng
B.S., Peking University

Jun Ho Yoon
B.S., Columbia University

Daniel Yuan
B.S., Johns Hopkins University, Pitt admit

Tianming Zhou
B.E., Tsinghua University

Ponzoni and Bahar published in PNAS

Structural dynamics is a determinant of the functional significance of missense variants

Abstract
Accurate evaluation of the effect of point mutations on protein function is essential to assessing the genesis and prognosis of many inherited diseases and cancer types. Currently, a wealth of computational tools has been developed for pathogenicity prediction. Two major types of data are used to this aim: sequence conservation/evolution and structural properties. Here, we demonstrate in a systematic way that another determinant of the functional impact of missense variants is the protein’s structural dynamics. Measurable improvement is shown in pathogenicity prediction by taking into consideration the dynamical context and implications of the mutation. Our study suggests that the class of dynamics descriptors introduced here may be used in conjunction with existing features to not only increase the prediction accuracy of the impact of variants on biological function, but also gain insight into the physical basis of the effect of missense variants.

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Please click here to view the full publication

“Protein Actions” book by Bahar and coworkers: APA Prose Award 2018 winner

“Protein Actions” book by Bahar, Jernigan and Dill, was selected amongst the APA Prose award 2018 winners in the category of Textbook/Biological and Life Sciences, by the Professional and Scholarly Publishing Division of the Association of American Publishers (see https://proseawards.com/winners/)

The PROSE Awards annually recognize the very best in professional and scholarly publishing by bringing attention to distinguished books, journals, and electronic content in 58 categories (see https://proseawards.com/) .

Bahar and Faeder labs publish in ENeuro

Heterogeneities in Axonal Structure and Transporter Distribution Lower Dopamine Reuptake Efficiency

Abstract

Efficient clearance of dopamine (DA) from the synapse is key to regulating dopaminergic signaling. This role is fulfilled by DA transporters (DATs). Recent advances in the structural characterization of DAT from Drosophila (dDAT) and in high-resolution imaging of DA neurons and the distribution of DATs in living cells now permit us to gain a mechanistic understanding of DA reuptake events in silico. Using electron microscopy images and immunofluorescence of transgenic knock-in mouse brains that express hemagglutinin-tagged DAT in DA neurons, we reconstructed a realistic environment for MCell simulations of DA reuptake, wherein the identity, population and kinetics of homology-modeled human DAT (hDAT) sub-states were derived from molecular simulations. The complex morphology of axon terminals near active zones was observed to give rise to large variations in DA reuptake efficiency, and thereby in extracellular DA density. Comparison of the effect of different firing patterns showed that phasic firing would increase the probability of reaching local DA levels sufficiently high to activate low-affinity DA receptors, mainly due to high DA levels transiently attained during the burst phase. The experimentally observed non-uniform surface distribution of DATs emerged as a major modulator of DA signaling: reuptake was slower, and the peaks/width of transient DA levels were sharper/wider under non-uniform distribution of DATs, compared to uniform. Overall, the study highlights the importance of accurate descriptions of extra-synaptic morphology, DAT distribution and conformational kinetics for quantitative evaluation of dopaminergic transmission and for providing deeper understanding of the mechanisms that regulate DA transmission.

 

Please click here to view the full study.