Responsibilities

Position Summary:

A position for Technical Associate II is open in the laboratory of the Wellstone Muscular Dystrophy Research Center, an NIH-designated center of excellence. This laboratory, directed by Dr. Charles Thornton, is recognized as a world leader for studies of genetic diseases and therapeutic development. The Wellstone Center in Rochester is the oldest of its kind, now in its 18 th year of NIH funding. Scientifically, the main focus is on genetic diseases caused by expanded repeats. These diseases involve repetitive segments of DNA that occur at several places in the human genome, which show unusual genetic instability, and have a strong tendency to grow larger over time in a single person, or when transmitted from parent to offspring. To mimic these diseases the lab has used CRISPR or other sorts of genetic engineering to insert expanded repeats into the mouse genome. Mice are then used to study the diseases and develop new treatments. At the same time, parallel studies are carried out on people who carry expanded repeats, who come to the UR Clinical Research Center. For example, studies are performed to determine why the repeats grow larger as people get older. Or, the lab studies cells and tissue samples to understand why expanded repeats cause problems with muscle and heart tissue. Much of this work involves detailed characterization of RNA. Finally, the lab is closely involved in developing new treatments. In fact, this work has reached the exciting stage where new treatments have been developed that show beneficial effects in mouse models, and are now advancing through the different phases of testing in people, including studies on our own Clinical Research Center. Overall, the position calls for high levels of experience, precision, and reliability, using methods that are varied, complex and non-routine. Current efforts are focused in three key areas:

1. Advanced genetic techniques to characterize repeats in DNA. These methods include DNA amplification, Southern blotting, and next generation sequencing. The sequencing methods make use of new technologies for long-read single-molecule sequencing. This role will be responsible for developing, optimizing and streamlining these methods, then applying them to analyze DNA samples from mouse and human studies. The human DNA samples will be collected from people who come to the Clinical Research Center, or are shipped to the lab from other sites. Samples need to be entered into a BioBank, then analyzed by several methods mentioned above, then the results are correlated with severity of symptoms that people experience.

2. Advanced procedures to analyze RNA. The lab is credited with discovery of a new type of disease process, called RNA toxicity, in which a genetic abnormality (expanded repeats) causes profound changes in RNA. This occurs in muscle, heart, and brain tissue, causing many symptoms. Cutting-edge analysis of RNA is a key activity for this position. Most commonly this will involve preparation of targeted RNA sequencing libraries for next generation sequencing. Molecular barcodes are applied to designate individual samples, so that dozens of samples can be analyzed in a single run of the sequencer. These methods are used to monitor how the diseases progresses over time and how it responds to treatment. Methods for performing this analysis are constantly evolving and new refinements will need to be developed.

3. Studying new treatments. New treatments are being developed within the lab and also by collaborators at other sites. Studies to assess their effectiveness will involve analysis of RNA samples that are extracted from heart or muscle tissue (mice) or muscle biopsy samples (people) or microscopic examination of muscle tissue using specialized procedures for fluorescence in situ hybridization. Some experiments also involve cell culture systems.

Typical Duties:

• Perform analysis of expanded repeats and other genetic variants in DNA. This includes isolation or amplification of DNA segments for measurement of repeat size by several methods, including capillary and gel electrophoresis, Southern blotting, and long-read single-molecule sequencing. The latter methods use several different sequencing platforms, and will require development of new methods and optimization of methods that currently exist. Also, high-throughput sequencing will be used to analyze single-nucleotide genetic variants. Results will be reviewed for quality control metrics and then organized for analysis by bioinformatic experts. Datasets and results will need to be generated for manuscript preparation and grant applications. 25%

• Analysis of RNA for alternative splicing and gene expression. This includes extracting RNA from tissue samples, synthesis of cDNA, and then preparation of libraries for targeted RNA sequencing. Including in this task is maintenance of biobanks and inventories of tissue samples, customization of procedures for preparing libraries, review of quality control metrics before submission to sequencing centers, interactions with staff at the sequencing centers (UR and elsewhere) to provide instructions for sequencing runs, review of results for sequencing efficiency, and interface with bioinformatics experts who perform subsequent analyses. Maintaining lab notebooks and sample logs for all experiments is a key activity. 20%

• Following approved protocols for the conduct of research, develops and installs laboratory operating procedures. Develops and modifies test methods, selects procedures for data collection and handling, and develops programs for conversions and statistical treatment of data. Analyze and evaluate experimental data and interpret results; assesses the importance of findings in relation to the general research program. Prepare written reports and assist in writing of the principal project report as well as the writing of articles for publication. 15%

• Perform other molecular biology protocols, such as, Western blots, DNA cloning, cell transfection. Although managing mouse colonies is not a core responsibility, cross-training for mouse research is desirable to accommodate peak loads and cross-coverage with other people in the lab. Experience with operation of a cryostat and preparation/processing of frozen sections for histologic analysis and in situ hybridization is desirable but not essential. 15%

• Training and oversight of undergraduate students and other lab staff working on experiments. Assist with training of graduate students and post-doctoral fellows. Counsel them on technical problems, advise and assist them with special research projects. Insures that health and safety practices are maintained in accordance with University policy and the law. 10%

• Assist with lab maintenance tasks including maintenance of laboratory space/reagents and writing protocols. Maintains inventory and equipment as needed and as directed by laboratory manager. Utilizes research literature to assist with developing new methods and experimental design. 10%

• Other projects and job duties as assigned. 5%

Requirements:

• Bachelor’s degree with course work in field of assignment, and at least 2 years of related work experience involving direct assistance to researchers; or any equivalent combination of experience, training, and education. At least 5 years of experience in research preferred.

• Must have strong attention to detail and have excellent interpersonal and communication skills with faculty, technical staff, postdocs, graduate students, undergraduate students and other labs.

• Must be highly organized, self-motivated individual capable of working independently in a collaborative setting.

How To Apply

All applicants must apply online.

EOE Minorities/Females/Protected Veterans/Disabled

Pay Range

Pay Range: $ 53,500 - $ 74,900 Annually

The referenced pay range represents the minimum and maximum compensation for this job. Individual annual salaries/hourly rates will be set within the job’s compensation range, and will be determined by considering factors including, but not limited to, market data, education, experience, qualifications, expertise of the individual, and internal equity considerations.

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Location: School of Medicine & Dentistry
Full/Part Time: Full-Time
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