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Heads of Laboratories

Head shot of Shixin Liu
Shixin Liu, Ph.D.
Assistant Professor
Laboratory of Nanoscale Biophysics and Biochemistry
Shixin.Liu@rockefeller.edu

Biomolecular complexes in the cell are often coupled to each other in time and space, giving rise to new forms of function and regulation. Using single-molecule and genome-wide techniques, Dr. Liu investigates the interaction, coordination, and competition among principal machineries involved in gene expression. The goal is to elucidate how cellular processes collectively respond to changing conditions during growth, development, and disease.

Virtually all aspects of the cellular life involve the operation of nanometer-scale machines, commonly known as molecular motors, which convert chemical energy into mechanical work. The advent of single-molecule techniques has made it possible to examine these tiny machines in unprecedented detail by following each individual walk, pull, and twist in real time. It is thus not surprising that, over the past decade, a soaring number of molecular motors have been subject to single-molecule interrogation, which uncovered a wealth of novel information and oftentimes unexpected phenomena.

However, much less attention has been paid to how these machines interact, and in many cases, cooperate. This represents a crucial next step toward connecting insights from in vitro experiments back to the cellular environment. Dr. Liu’s research takes this step, using state-of-the-art single-molecule tools, sometimes in combination with genomic approaches, to understand how motor-driven processes are integrated into a coherence network in the cell and how their interplay evolves in response to environmental changes.

Through his training, Dr. Liu has established an expertise in two primary classes of single-molecule methods: fluorescence-based detection and force-based manipulation. As a graduate student at Harvard University, he used single-molecule fluorescence spectroscopy to examine the movement of HIV reverse transcriptase, the target of many anti-AIDS therapies, as it makes a DNA copy of viral RNA. During his postdoc, Dr. Liu utilized high-resolution optical tweezers to investigate the bacteriophage 29 DNA packaging motor, which is a ring-shaped ATPase, a common type of molecular motor. His research revealed the precisely coordinated chemical and mechanical transitions that its five ring subunits must undergo, as well as an unexpected division of labor among these subunits, insights that likely apply to many molecular motors with similar structures.

Dr. Liu’s current research focuses on the fundamental gene expression process, during which a series of molecular machines acts in concert to convert genetic DNA code into RNA messages and eventually protein products. His laboratory has a few specific interests. The first is the interplay between bacterial transcription, translation, and RNA degradation machineries, which controls the fate of RNA transcripts and the output of protein synthesis.

The second area of focus for the Liu lab lies within more complex eukaryotic cells. Dr. Liu is designing experiments to investigate how RNA polymerase reads through eukaryotic chromatin, a process altered by transcription factors, the remodeling of chromatin, and epigenetic modifications. And, finally, Dr. Liu is interested in the collisions between the machinery responsible for replicating DNA and that responsible for transcribing it. Such conflicts occur in both prokaryotes and eukaryotes and could lead to DNA damage and mutagenesis. The Liu lab is seeking to visualize these collisions, as well as the strategies used by the cell to resolve them, and the fates of the machines involved.

Liu is a faculty member in the David Rockefeller Graduate Program, the Tri-Institutional M.D.-Ph.D. Program, and the Tri-Institutional Ph.D. Program in Chemical Biology.


EDUCATION

B.S. in biology, 2003
University of Science and Technology of China 

Ph.D. in chemistry, 2009
Harvard University

POSTDOC

University of California, Berkeley, 2010–2015

POSITIONS

Assistant Professor, 2015–
The Rockefeller University

AWARDS

National Institutes of Health Pathway to Independence Award, 2013

SELECTED PUBLICATIONS

Liu, S. et al. A viral packaging motor varies its DNA rotation and step size to preserve subunit coordination as the capsid fills. Cell 157, 702–713 (2014).

Dangkulwanich, M. et al. Complete dissection of transcription elongation reveals slow translocation of RNA polymerase II in a linear ratchet mechanism. Elife 2, e00971 (2013).

Chistol, G. et al. High degree of coordination and division of labor among subunits in a homomeric ring ATPase. Cell 151, 1017–1028 (2012).

Liu, S. et al. Initiation complex dynamics direct the transitions between distinct phases of early HIV reverse transcription. Nat. Struct. Mol. Biol. 17, 1453–1460 (2010).

Liu, S. et al. Slide into action: dynamic shuttling of HIV reverse transcriptase on nucleic acid substrates. Science 322, 1092–1097 (2008).