Postdoctoral Fellowship: Exploring RNA Metabolism in Neurodegenerative Disease
Exploring RNA Metabolism in Neurodegenerative Disease
Job Description: An NIH funded postdoctoral position is available in the laboratory of Benjamin Wolozin, M.D., Ph.D., to study the molecular basis of neurodegenerative disease (https://sites.bu.edu/wolozinlab/). The laboratory investigates the role of RNA binding proteins in the pathophysiology of neurodegenerative diseases, including Alzheimer disease, amyotrophic lateral sclerosis (ALS) and Parkinson disease.
We are initiating new programs that focus on characterizing the role of modified RNA species (e.g., methylated RNA such as N6-methyladenosine) and non-coding RNAs (e.g., circular RNA) in disease. The first stage of this work is described in our recent publication (Jiang, et al, Interaction of tau with HNRNPA2B1 and N6-methyladenosine RNA mediates the progression of tauopathy. Mol. Cell (2021), PMID 34453888). The work is expanding out to explore these biological systems further using approaches such as CRISPR, m6A RIPseq and proteomics (coupled with TurboID proximity profile labeling technologies), as well as applying the work towards diagnostics and therapeutics.
The laboratory employs advanced disease models that are used for these explorations. We have developed a 3D human iPSC model system that incorporates human neurons, astrocytes and microglia in spheroids that develop major elements of the pathophysiology of Alzheimer’s disease. These assembloids are also being adapted to enable study of ALS and Parkinson disease. The animal models used in the laboratory utilize knockin of specific disease linked genes, such as amyloid precursor protein, with crossing to other disease linked genes. We also have developed inducible cell type selective conditional knockout mouse lines.
Upon joining my laboratory, the postdoctoral candidate will focus on studies of neurodegenerative disease, ranging from in vitro studies of liquid-liquid phase separation, to analysis of splicing and translation, to investigation of animal or human (iPSC/organoid) models of disease. Approaches utilize live imaging, proteomics, systems biology, viruses and synthetic biology. Recent studies explore the roles of RNA binding proteins and RNA metabolism in neurodegenerative diseases: Jiang, et al, Mol. Cell, PMID 34453888, Ash, et al, PNAS 2021, PMID 33619090, Apicco, et al, Nature Neuro., 2018, 21(1):72-80, PMID: 29273772; Jiang et al, Acta Neuropath. 2019, 137(2):259-77. PMID 30465259), Pourhaghighi, et al, Cell Systems, 2020, 10(4):333-350. PMID: 32325033.
- Animal models of Alzheimer’s disease, ALS and Parkinson disease: Mechanisms
- RNA metabolism: RNA binding proteins, RNA methylation, RNA translation, RNAseq, eCLIP, RNA splicing and proteomics
- Human iPSCs/spheroids and brain: biomarkers and therapeutic approaches
Desired Skills: Any of the skills below would be helpful for this position.
- Gene delivery, viruses, over-expression, knockdown, CRISPR
- Biochemistry and protein aggregation
- Immunohistochemistry, Immunoprecipitation, immunoblotting
- Molecular Neuropathology
- Systems Biology
- Neuronal culture: primary neuron culture, iPSCs and cell lines
- Live cell imaging and Super-resolution imaging
About the employer: The laboratory is well funded and positions are available immediately. Boston University School of Medicine is located in the heart of one of the world’s most vibrant biotechnology communities. The laboratory is a moderate sized lab (~10 people), with 2200 square feet of space, with all necessary resources.
Highest priority will be given to candidates who are about to finish their Ph.D., or within 1 year of finishing their Ph.D. (i.e., early postdocs). For more information, visit the Wolozin Lab website: https://sites.bu.edu/wolozinlab/