School/Unit Harvard Medical School Sub-Unit ------------ Location USA - MA - Boston Job Function Research Time Status Full-time Department Genetics Salary Grade 056 Union 00 - Non Union, Exempt or Temporary Duties & Responsibilities Harvard Medical School seeks a highly motivated Researcher for a full-time position. We are seeking an experienced (Ph.D. or beyond) individual to do experimental research in modern molecular neurogenetics. The individual will design and carry out experiments in the Gray lab, which studies long-term memory consolidation and neuronal activity-regulated transcription in mice. Experience, by altering the activity patterns of neurons, leads to transcriptional changes that shape circuit development and consolidate short-term memories into life-long ones. These activity-regulated transcriptional changes are required not only for adaptive but also for non-adaptive information storage, which underlies addiction and post-traumatic stress disorder. It has long been known that activity-regulated transcription depends on calcium- and cyclic AMP-dependent signal transduction cascades. These cascades culminate in the activation of at least 30 neuronal activity- regulated transcription factors. The transcription factors include those that are covalently modified upon neuronal activation (e.g., CREB), as well as immediate early gene (IEG) transcription factors that are transcribed and translated in response to activity (e.g., EGR1). Activity-regulated transcription factors induce hundreds of activity-regulated genes, several of which (e.g., Arc, Bdnf) have established functions in neuronal plasticity and development. However, a major gap in our understanding of the activity-regulated transcriptional network involves the precise relationship between activity and gene expression. This input-output relationship has so far been impossible to define in vivo, and in vitro studies have focused on all-or-nothing, on-off neuronal activation. Thus, despite the central importance of neuronal spiking frequencies and patterns to information processing in the nervous system, almost nothing is known about whether or how neuronal activity is interpreted quantitatively by the genome.
The long-term goal of the Gray laboratory is to understand how neuronal activity acts through transcription to enable information consolidation in the brain. An essential step in this effort is to determine the mechanisms by which the activity-regulated transcriptional network interprets neuronal activity quantitatively. The successful candidate will spearhead this effort, including assembling and submitting a publication within the first year of their tenure. The initial set of experiments will include mouse brain dissections, primary neuronal cell culturing, and molecular biology. The successful applicant will also apply a recently-developed technology (Massively Parallel Reporter Assays) that makes possible simultaneous analysis of thousands of regulatory elements.
Please go to Dr. Gray's webpage at http://genetics.med.harvard.edu/gray/ for more information. Basic Qualifications Ph.D. degree in biology, genetics, or physical sciences. Molecular biology skills and experience required. Additional Qualifications Laboratory experience in genetics, molecular biology , or neurobiology. Particularly relevant laboratory experience includes: (i) construction of genomic libraries for large-scale DNA sequencing; (ii) real-time PCR; (iii) DNA extraction and analysis; (iv) molecular cloning; and (v) brain dissection, surgery, and sectioning, (vi) electrophysiology, (vii) in situ hybridization, (viii) immunohistochemistry. Familiarity with advanced laboratory techniques and principles of molecular biology. Additional qualifications include: excellent written and oral communication abilities; computer proficiency; strong organizational skills, including the ability to multi-task; ability to work in teams in a fast-paced, dynamic environment. Additional Information Offer contingent upon successful completion of a pre-placement medical evaluation.
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