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High-throughput screening platform for small-molecules with anti-inflammatory potential

High-throughput screening platform for small-molecules with anti-inflammatory potential 2020-2022
Acronym: HTS-IL-1β
Project director: Mari Chiritoiu

This project aims to develop a sensitive high-throughput screening platform by generating an endogenously tagged interleukin-1β reporter cell line by CRISPR-Cas9 technology, able to monitor stimulated IL-1β secretion with the purpose to identify new chemical compounds with anti-inflammatory activity that will be validated in primary macrophages and a mouse model for sepsis.

Background: The immune system is the main pillar of the human body’s health. Accurate understanding of the immune modulators will enable us to precisely unveil the abilities of the immune system to fight virtually all human diseases. Chronic inflammation is the hallmark of many human pathologies including cancer and currently, anti-inflammatory therapy is focused on inhibiting production of eicosanoid mediators of inflammation (prostaglandings, thromboxanes, prostacyclins, leukotrienes) by inhibiting their producing enzymes (COX-1/2). Although efficient, recent discoveries emphasized potentially dangerous side effects of these drugs. Therefore, identification and validation of new molecules with anti-inflammatory potential and reduced side effects, becomes of major importance. In the recent years the development of molecules targeting signaling pathways involved in production and release of pro-inflammatory mediators, such as cytokines and chemokines, has gained field and forwards the concept of new-age therapies.

Hypothesis: Our hypothesis is that identifying small molecules, which target the production or secretion of pro-inflammatory cytokines from macrophages and monocytes, such as interleukin-1β (IL-1β), will provide an improved alternative for treating chronic inflammation associated with numerous pathologies.

Aim: This project aims to develop a sensitive high-throughput screening platform by generating an endogenously tagged interleukin-1β reporter cell line by CRISPR-Cas9 technology, able to monitor stimulated IL-1β secretion with the purpose to identify new chemical compounds with anti-inflammatory activity that will be validated in primary macrophages and a mouse model for sepsis.


Expected results: Implementation of this project will deliver a versatile screening platform for anti-inflammatory compounds and a list of validated small molecules with anti-inflammatory properties, which can be easily translated to pre-clinical studies.

Mari Chiritoiu, PhD
Mari Chiritoiu, PhD

Senior Reseacher III

Mari Chiritoiu graduated from Faculty of Chemistry, University of Bucharest (2004-2008) and received her Ph.D. in Biology from the Institute of Biochemistry of the Romanian Academy in 2014, under the supervision of dr. Stefana Petrescu. She was a posdoctoral fellow in the lab of prof. Vivek Malhotra, at CRG-Centre for Genomic Regulation, Barcelona, Spain (2016-2019) where she investigated the process of unconventional protein secretion using as model cargo the pro-inflammatory cytokine interleukin-1β. In the future, dr. Chiritoiu aims to understand key aspects of the molecular mechanism of leaderless protein export, such as interleukin-1β and α-synuclein, More...

Costin-Ioan Popescu, PhD
Costin-Ioan Popescu, PhD

Scientific Researcher II

Dr. Costin-Ioan Popescu is leading the Hepatitis C Virus group in the Department of Viral Glycoproteins of the Institute of Biochemistry of the Romanian Academy. Costin-Ioan Popescu defended his PhD thesis at University of More...

Laura-Georgiana Manica, PhD Student
Laura-Georgiana Manica, PhD Student

PhD Student

2016 - present: Ph.D. Student at Institute of Biochemistry of the Romanian Academy; 2016 - present: Resident Pharmacist in Pharmaceutical Laboratory at Emercency University Hospital Bucharest; 2011 - 2016: M.Sc. and B.Sc More...

Laurentiu Spiridon, Dr.
Laurentiu Spiridon, Dr.

Laurentiu Spiridon is a researcher in the Institute of Biochemistry of the Romanian Academy. Laurentiu is currently working in Bioinformatics & Structural Biochemistry in the Bioinformatics & Structural Biochemistry.

Simona Ghenea, Dr.
Simona Ghenea, Dr.

Researcher

Simona Ghenea is a researcher in the Institute of Biochemistry of the Romanian Academy. Simona is currently working in Molecular Cell Biology in the Molecular Cell Biology.

Stefana-Maria Petrescu, Dr.
Stefana-Maria Petrescu, Dr.

Director of Institute, Head of Department

Dr. Petrescu graduated from the Department of Biochemistry, University of Bucharest and obtained a PhD in Biology from the Romanian Academy. She was a DAAD fellow and FEBS fellowship recipient at University of Wurzbur More...

Coordinator: The Institute of Biochemistry of the Romanian AcademyRomania;

Director: Dr. Marioara Chiritoiu-Butnaru

Team members: 

Dr. Stefana Petrescu

Dr. Costin-Ioan Popescu

Dr. Simona Ghenea

Dr. Laurentiu Spiridon

PhD student: Laura Georgiana Manica

 

Partner 1: Institutul National de Cercetare Dezvoltare in Domeniul Patologiei si Stiintelor Medicale "V. Babes"; 

Project responsible: Dr. Gheorghita Isvoranu

Team members: 

Researcher: Mihaela Surcel

Researcher: Adriana-Narcisa Munteanu

Technician: Gina Simion

Technician: Mihaela Munteanu

Technician: Magdalena Dumitru

Technician: Elena-Cristina Munteanu