These two full-time Postdoctoral Research Associate positions will study autophagy and its roles in growth and development, nutrient recycling, and maintenance of protein homeostasis. It is now becoming clear that autophagy is a major player in the selective turnover of individual proteins, protein complexes, protein aggregates, organelles and even invading pathogens. Using yeast, Arabidopsis and maize as tractable genetic and biochemical models, the Vierstra lab is attempting to define the mechanisms that drive selective autophagy and understand how this process influences an organism’s proteome and metabolome during development and under nutrient-rich and starvation conditions, using a suite of omics approaches, including mass spectrometric methods to globally interrogate changes in the protein composition of an organism.
The goal of the NIH-funded project is to understand selective autophagy using a novel collection of autophagy receptors we recently discovered that employ an ATG8-binding UIM domain to tether substrates to enveloping autophagic vesicles. Two important targets of these UIM receptors are proteasomes and CDC48/p97, which become substrates for autophagy upon chemical inhibition or genetic inactivation. Turnover of proteasomes (proteaphagy) is of particular interest as its degradation is regulated by a series of ubiquitylation events and involves at least two types of biomolecular condenstates before deposition of proteasomes into vacuoles/lysosomes for degradation. As the CDC48/p97 mutants that initiate their autophagy have been linked to a variety of neuropathogies, understanding this turnover has medical relevance. The second project recently funded by NSF involves exploiting metabolomic, proteomic, transcriptomic and ionomic analyses on a collection of maize atg mutants impacting various steps in autophagy to understand how this system regulates intracellular recycling and helps maintain proteostasis. Central to this work is an in-house ThermoFischer Q-Exactive mass spectrometer that enables deep proteomic analyses at a quantitative level to provide overviews of how proteomes are affected and adjust to defects in autophagy. For more background on these topics and information about experimental approaches, see recent papers. The series of Marshall et al. (2015) Mol. Cell; Marshall et al. (2016) Cell Rep.; Marshall and Vierstra (2018) eLife; and Marshall et al. (2019) Cell (in press) papers provides a background on the UIM-based autophagic system for proteasome and CDC48/p97 turnover. For the omics work and other studies on autophagy in plants, see papers by Li et al. (2015) Plant Cell; McLoughlin et al. (2018) Nat. Plants; and Liu et al. (2018) Front. Plant Sci. A general review on the topic is provided by Marshall and Vierstra (2018) Annu. Rev. Plant Biol. These projects not only offer exciting science but also the ability to become proficient in modern proteomic and genetic approaches and network analysis.
Washington University in St. Louis is a center of excellence in all aspects of biology with a special emphasis on plant science, and includes modern facilities and instrumentation necessary for the work. In addition, both the Danforth Plant Science Center and companies such as Bayer Crop Sciences (formally Monsanto) are near by to make St. Louis an attractive place to do plant research with lots of technical expertise available, while the nearby WashU Medical School offers expertise and collaborators in various medically-relevant autophagic processes.
PRIMARY DUTIES AND RESPONSIBILITIES:
- Design, set up, and perform experiments related to understanding how autophagy regulates eukaryotic development, provides protection against nutritional stress, and directs intracellular recycling at the molecular level. Propose new directions and possible next steps. Coordinate efforts among concurrent experiments. Collect data and perform analysis. Ensure the continuity of our germplasm, lab strains, and experimental colonies.
- Prepare scientific data and manuscripts for publication.
- Help prepare grant proposals to support the research.
- Attend and present research progress at national and/or international meetings on the topics
- Promote discussion among laboratory members, implement changes to protocols. This will require adaptation and development of new protocols as the research progresses.
- Train and manage undergraduates and graduate students in conducting the research.
- Quality control: Help oversee all autophagy-related projects and enforce the highest standards of quality and research conduct.
- Produce and maintain lab notebooks and insure periodic back up of all data.
- Maintain and organize the collection of germplasm and stock cultures affecting various autophagy components, reporters and substrates
- Maintain and organize the extensive proteomic datasets generated from the mass spectrometric studies.
Required Qualifications: Ph.D in Biology.
- Ph.D in biochemistry, genetics, molecular biology, or related fields.
- Excellent organizational and data management skills.
- Attention to detail.
- Proficiency with computers.
- Experience with various molecular and genetic techniques in yeast and/or plants, and a broad background with maize is helpful for the NSF-funded position.
- Experience with proteomic approaches involving mass spectrometry and NexGen sequencing, and an understanding of the basic statistical and data analyses associated with these large datasets are also advantageous.
- Experience with recombinant DNA methods, expressing proteins in various expression systems, protein purification, and experience with NextGen Sequencing methods are helpful.
- If needed, successful candidate will be trained in mass spectrometry and other proteomic-based approaches.
- Ability to work well within a group, and to handle multiple concurrent assignments is essential.
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