The England Laboratory within the Department of Pharmaceutical Chemistry seeks candidates for a Specialist research position with expertise in cellular and molecular biology. Qualified applicants will be hired at the Junior, Assistant, or Associate level, depending upon the candidate’s experience. Dr. England’s research is focused on developing chemical probes and potential drug leads for nuclear receptors, a class of intracellular proteins that regulate gene expression in response to endogenous hormones and other small molecules. These receptors play critical roles in human development, physiology, and disease and have proven to be effective therapeutic drug targets. Under general direction, the incumbent will characterize the activity of ligands targeting the nuclear receptor Nurr1, a potential therapeutic target for Parkinson’s disease, and LRH-1, a potential therapeutic target for several cancers. The incumbent will also design and utilize constructs to study the oligomerization of these nuclear receptors with intracellular proteins. Applicants are expected to be able to work independently and possess the ability to read and digest literature surrounding their project, and to troubleshoot experiments when they don’t work. In addition, the applicant must possess the ability to analyze their data and clearly communicate their research techniques and results in written and oral formats suitable for publication. Specific activities associated with the position include, but are not limited to, the following:
Cellular assays (cultured cells). Technical skill set: aseptic cell culture procedures, DNA cloning, primer design for PCR, rtPCR, qPCR.
Cellular assays (neurons). Technical skill set: preparation of acute dissociated neurons from mice.
Cellular imaging assays. Technical skill set: live and fixed cell imaging.
Specialists appointed at the junior rank must possess a baccalaureate degree (or equivalent degree).
Specialists appointed at the Assistant or Associate rank must possess a master’s degree (or equivalent degree) or five to ten years of research experience.
Two or more years prior experience conducting laboratory research.
Excellent organizational skills
Excellent written and verbal presentation skills
Experience with graphing software (e.g. Excel, Prism or KaleidaGraph) and statistical analyses, powerpoint or other oral presentation software.
Applicants must list all of the basic qualifications (or if pending) on their CV and/or cover letter upon submission.
Candidates must meet the requirements by the time of appointment.
PhD (or equivalent level of experience) in cellular and molecular biology, biochemistry, neuroscience, or equivalent area.
UC San Francisco seeks candidates whose experience, teaching, research, or community service that has prepared them to contribute to our commitment to diversity and excellence. The University of California is an Equal Opportunity/Affirmative Action Employer. All qualified applicants will receive consideration for employment without regard to race, color, religion, sex, sexual orientation, gender identity, national origin, disability, age or protected veteran status.
Amendment to Job Description for Focus on COVID-19 Research SARS-CoV-2 is a deadly coronavirus that infects humans primarily via the nasal route causing symptoms that range from mild (fever, cough and runny nose) to severe, including acute respiratory distress and, in some cases, death due to respiratory failure. The clinical manifestations and severity of the infection are driven by the innate immune response which causes an increase in proinflammatory cytokines. While the pathogenic outcomes of the SARS-CoV-2 infection are mainly due to effects on the respiratory system, mounting evidence reveals the virus also infects other organs including the brain.1-4 Once the virus enters the central nervous system, it triggers a neuroinflammatory response leading to activation of microglia and astrocytes, release of cytokines, and altered brain homeostasis resulting in neuronal death.5 Neuroinflammation with increased cytokine activity is commonly associated with neurodegenerative diseases such as Parkinson’s disease, Alzheimer’s disease and ALS. Thus, it is plausible that infection with SARS-CoV-2 leads to a neuroinflammatory reaction in the central nervous system that renders the brain more vulnerable to neurodegeneration.6-7 One of the key players in the pathology of Parkinson’s disease and other neurodegenerative disorders is the nuclear receptor Nurr1, a ligand-activated transcription factor expressed in the brain. Nurr1 is critical for the development, maintenance and survival of dopaminergic neurons. Moreover, Nurr1 is expressed in glial cells where it plays an essential anti-inflammatory role in the brain by inhibiting expression of proinflammatory cytokines and preventing neuronal death. Qualified candidates for this position will investigate whether infection of iPSC-derived dopaminergic neurons and/or neuron-derived cell lines with SARS-CoV-2 alters Nurr1 levels and activity in these cells and/or causes inflammation-induced phenotypes such as altered expression of immune genes, increased apoptosis, altered autophagy and oxidative stress. Furthermore, the candidate will investigate whether Nurr1 agonists previously developed in the England lab may be used to increase expression of anti-inflammatory genes in neuronal cells. These studies will insight into the role Nurr1 may play in mitigating neuroinflammation related to cytokine storm, and possible neurodegeneration, induced by SARS-CoV-2 infection and offer a means of mitigating harmful effects of the virus in the brain.
Literature Associated with the COVID-19 Amendment (1) Steardo, L.; Steardo, L., Jr.; Zorec, R.; Verkhratsky, A., Neuroinfection may contribute to pathophysiology and clinical manifestations of COVID-19. Acta Physiol (Oxf) 2020, 229 (3), e13473. (2) Huang, J.; Zheng, M.; Tang, X.; Chen, Y.; Tong, A.; Zhou, L., Potential of SARS-CoV-2 to Cause CNS Infection: Biologic Fundamental and Clinical Experience. Front Neurol 2020, 11, 659. (3) Payus, A. O.; Liew Sat Lin, C.; Mohd Noh, M.; Jeffree, M. S.; Ali, R. A., SARS-CoV-2 infection of the nervous system: A review of the literature on neurological involvement in novel coronavirus disease-(COVID-19). Bosn J Basic Med Sci 2020, 20 (3), 283-292. (4) Zhou, Z.; Kang, H.; Li, S.; Zhao, X., Understanding the neurotropic characteristics of SARS-CoV-2: from neurological manifestations of COVID-19 to potential neurotropic mechanisms. J Neurol 2020, 267 (8), 2179-2184. (5) Kanberg, N.; Ashton, N. J.; Andersson, L. M.; Yilmaz, A.; Lindh, M.; Nilsson, S.; Price, R. W.; Blennow, K.; Zetterberg, H.; Gisslen, M., Neurochemical evidence of astrocytic and neuronal injury commonly found in COVID-19. Neurology 2020. (6) Serrano-Castro, P. J.; Estivill-Torrus, G.; Cabezudo-Garcia, P.; Reyes-Bueno, J. A.; Ciano Petersen, N.; Aguilar-Castillo, M. J.; Suarez-Perez, J.; Jimenez-Hernandez, M. D.; Moya-Molina, M. A.; Oliver-Martos, B.; Arrabal-Gomez, C.; Rodriguez de Fonseca, F., Impact of SARS-CoV-2 infection on neurodegenerative and neuropsychiatric diseases: a delayed pandemic? Neurologia 2020, 35 (4), 245-251. (7) Heneka, M. T.; Golenbock, D.; Latz, E.; Morgan, D.; Brown, R., Immediate and long-term consequences of COVID-19 infections for the development of neurological disease. Alzheimers Res Ther 2020, 12 (1), 69.
Internal Number: JPF02871
About University of California, San Francisco
The University of California, San Francisco (UCSF) is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and high-quality patient care. It is the only UC campus in the 10-campus system dedicated exclusively to the health sciences.