PRR Project

Summary

Job Description:We are looking for a talented toxicologist to conduct research in the development of new P-gp activators/inducers, with a specific focus on overcoming a dysfunctional P-gp at the BBB, a pathological mechanism occurring in distinct neurodegenerative diseases (NDs). The project will have a special focus on Alzheimer’s Disease (AD), which has as the major pathological hallmark the brain deposition of the neurotoxic amyloid-ß peptide (Aß), a known P-gp substrate. The role will involve the development/screening of new compounds with the potential to increase P-gp expression/activity, limiting the accumulation/toxicity of Aß and other neurotoxic P-gp substrates. The position will contribute to the development of innovative strategies for counteracting Aß-mediated neurodegeneration, an approach that can also be successfully applied to the treatment/prevention of other NDs where a defective P-gp was also observed.Responsibilities:Lead and contribute to the preparation of grant applications and secure funding for research initiatives focused on the discovery of new P-gp activators/inducers.Screening of the effects of new compounds on P-gp expression/activity, using in vitro models of the BBB.Evaluation of the impact of P-gp activators/inducers in the toxicity of P-gp substrates, including Aß, using in vitro disease models. Identification of the most promising compounds to be patented.Stay up-to-date on cutting-edge methods and tools to identify P-gp activators/inducers and evaluate their efficacy.Establish collaborations with interdisciplinary teams to advance the identification of innovative P-gp activators/inducers.Supervise undergraduate and graduate students at master´s and PhD levels, and manage mentorship of junior researchers.Engage in technology transfer initiatives.Disseminate findings through high-impact publications, patent filings, and presentations at conferences and public engagements.Scientific profile:The ideal candidate should have a strong background in toxicology, in vitro studies, drug discovery, toxicokinetics, and P-gp. Additionally, expertise in cell culture, in vitro disease models, neurotoxicity, neuroprotection studies, cell biology, and analytical techniques is essential. A solid understanding of P-gp´s protective role and impact at the BBB is required. A PhD in Toxicology, Pharmaceutical Sciences, or a related field, with a speciality in Toxicology or a closely related discipline, is preferred, along with a publication record in the scientific area of this application. Experience in supervising pre- and postgraduate students is important. Excellent communication skills, including proficiency in public engagement and scientific dissemination, are also necessary, including outreach activities.Rationale:The recruitment of UCIBIO/i4HB Chair in P-gp activators/inducers mining is in line with UCIBIO´s/i4HB strategy of translating research into future products and patient care.  This work falls under the UCIBIO thematic line of "Diagnostics, Drug Discovery and Development”, which is dedicated to finding innovative therapies for incurable diseases, through target characterization/identification of new biologically active molecules, which requires a multidisciplinary approach, a defining characteristic of our Unit.AD is one of the most prevalent NDs that affects millions of people worldwide, with prevalence and incidence increasing with age. This is even more fundamental as the available therapies remain limited and focused on symptom relief, with no drug currently available to delay/stop disease progression. Aß accumulation within the brain is thought to be the initial pathogenic trigger leading to progressive neuronal dysfunction. Furthermore, an insufficient P-gp-mediated Aß export was reported to be involved in AD initiation/progression. Thus, export mechanisms that are deficient in affected elderly represent new targets for AD treatment/prevention and, as such, the use of P-gp activators/inducers to efficiently restore a dysfunctional P-gp holds a significant potential to counteract Aß-mediated neurodegeneration.UCIBIO values the confluence of different scientific perspectives, and the addition of a toxicologist expert with experience in underscoring new P-gp inducers/activators to reduce the toxicity of harmful P-gp substrates will significantly enhance our capacity for innovative research, collaborative excellence, and scientific breakthroughs in tackling incurable diseases. The role is crucial to UCIBIO´s strategic vision, which aims not only to expand our knowledge but also to translate these findings into effective healthcare solutions.