Post Doctoral.Post Doctoral.Associate

SUMMARY

The Laboratory of Dr. Jonathan Coleman in the Department of Structural Biology is recruiting newly graduated, innovative, highly independent, and motivated candidates with structural biology and membrane protein backgrounds to fill a Postdoctoral Position. The Coleman lab primarily studies neurotransmitter transport proteins found in synaptic vesicles (SVs). Decades of research and drug development have shown that many diseases and disorders can be treated using drugs that modulate neurotransmitter availability. Many of these therapeutics block neurotransmitter reuptake or antagonize receptor signaling by acting on plasma membrane transporters and receptors. SVs store neurotransmitters in presynaptic neurons, which are released into the synapse to propagate neuronal signaling. SV transport proteins are also required for neurotransmitter release as they load neurotransmitters into SVs, rendering them fundamental components in the regulation of neurotransmitter signaling. Our work will provide a detailed and comprehensive understanding of the molecular mechanisms of SV transporter function. Vesicular monoamine transporter 2 (VMAT2) is the only transporter expressed in the central nervous system that loads biogenic amine-containing neurotransmitters such as dopamine, serotonin, and norepinephrine into SVs. Our studies will illuminate the molecular mechanisms of VMAT2 in neurons and reveal the structural basis for how inhibitors and substrates bind. The candidate will 1) Determine the structural basis of reserpine inhibition; 2) Demonstrate how neurotransmitters and amphetamines are transported by VMAT2 by determining structures in various substrate-bound and apo-conformational states. Our anticipated results will deepen our understanding of neurotransmitter binding and membrane transport mechanisms and provide necessary atomic information about this family of proteins, localization of the molecular determinants, and modes of drug interaction to guide the development of new inhibitors with fewer side effects and greater specificity. Ongoing works are examining the molecular mechanisms of transport and inhibition of VMAT2 using functional analysis and cryoEM. Recent publications include the cryoEM structure of VMAT2 complexed with the inhibitor tetrabenazine: https://elifesciences.org/reviewed-preprints/91973

The Department of Structural Biology in which Dr. Coleman is appointed is one of several foundational science Departments within the University of Pittsburgh School of Medicine. The Department, which was established in 2005 and is headed by Prof. Angela Gronenborn, is focused on applying NMR, X-ray crystallography, and Cryo-electron microscopy, as well as other accompanying biophysical tools, for understanding structure-function relationships of biological macromolecules. The Department has 9 full-time faculty with research interests that range from the structural biology of AIDS-related proteins, disease-related protein aggregates, such as Huntington and cataracts, human viruses, DNA replication machinery, bacterial chemotaxis, ion channels, G-protein coupled receptors, and receptor signaling complexes. The PI is a newly appointed Assistant Professor and also a member of the joint University of Pittsburgh/Carnegie Mellon Molecular Biophysics and Structural Biology (MBSB) Graduate Program, which includes 45 training faculty from 13 different academic departments.

Applicants should have an excellent track record with peer-reviewed publications, and possess a PhD, MD, or equivalent degree in the biomedical or related field. Candidates with relevant experience are preferred.

DUTIES RESPONSIBILITIES

Carry out independent projects to study the mechanisms of VMAT2

Publish scientific articles

Present at scientific conferences

Apply for fellowship, scholarship, and other grants

Train graduate students

Assist the Principal Investigator (PI) in managing the lab

QUALIFICATIONS AND EXPECTATIONS

Newly graduated

Innovative

Highly independent and motivated

Molecular and cellular biology background

Excellent track record with peer-reviewed publications

Possess a PhD, MD, or equivalent degree in the biomedical or related field

OPPORTUNITIES AVAILABLE

Study the mechanisms of VMAT2 using a combination of functional analysis, computational methods, and structural biology

Collaboration with computational biologists

Receive world-class training and have the opportunity to collaborate with diverse investigators

Collaborate with scientists across all schools of the University of Pittsburgh and around the world

WEBSITE

https://www.colemanlab.structbio.pitt.edu/

 
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