Post-Doc in molecular biology/origin of life (H/F)

ESPCI Paris

The “École Supérieure de Physique et de Chimie Industrielles de la Ville de Paris” (ESPCI Paris PSL) is a “Grande École d’Ingénieurs” with a strong international reputation for research (6 Nobel Prizes) and a member of the Université PSL (Paris Sciences & Lettres). ESPCI is a highly multidisciplinary environment with teaching and research in physics, chemistry, and biology. The project will be directed by Prof. Andrew Griffiths.

Prof. Andrew Griffiths’ Lab

The Laboratory of Biochemistry (LBC), directed by Prof. A. Griffiths, is a multidisciplinary laboratory spanning physics, chemistry, and biology. The unifying theme of their research is the use of microfluidic systems, and in particular droplet microfluidic systems, to answer questions in the field of biology and for the development of biotechnology applications. Three main areas of fundamental research can be distinguished: i) the emergence of Darwinian chemical systems (origin of life), ii) Darwinian system dynamics and directed evolution, and iii) single-cell analysis and screening. There is great synergy between fundamental research and applied projects, and this has resulted in the creation of several start-ups.

How did translation emerge in an RNA world? Ribozymes catalyzing peptide bond formation have been found by directed evolution [1] and very recently using highly conserved small RNA regions at the core of the ribosome [2]. This suggests that an origin of translation is possible from rudimentary RNAs. However, there remains a large gap between catalyzing a single peptide bond and establishing a genetic code.

The project aims to design, screen and evolve ribozymes that catalyze peptide bond formation from a aminoacylated RNAs with substrate specificity. The postdoc will then expand the repertoire of ribozymes and their specific charged RNAs. This should allow reaction networks made of multiple RNA species to catalyze the non-random synthesis of small peptides. In parallel, small peptides that improve ribozyme function will be screened for, with the ultimate goal to establish a positive feedback between peptide products formation and ribozyme catalysis.

The postdoc will benefit from expertise in the lab for directed evolution, microfluidics, sequencing, molecular design using machine learning.

[1] Zhang, B., & Cech, T. R. (1997). Peptide bond formation by in vitro selected ribozymes. Nature, 390(6655), 96-100.

[2] Bose, Tanaya, et al. "Origin of life: Protoribosome forms peptide bonds and links RNA and protein dominated worlds." Nucleic acids research 50.4 (2022): 1815-1828.

Related publications from the lab :

Lu, Heng, et al. "Small-molecule autocatalysis drives compartment growth, competition and reproduction." Nature Chemistry (2023): 1-9.

Reed, Brian D., et al. "Real-time dynamic single-molecule protein sequencing on an integrated semiconductor device." Science 378.6616 (2022): 186-192.

Ameta, Sandeep, et al. "Darwinian properties and their trade-offs in autocatalytic RNA reaction networks." Nature Communications 12.1 (2021): 842.

Arsène, Simon, et al. "Coupled catabolism and anabolism in autocatalytic RNA sets." Nucleic Acids Research 46.18 (2018): 9660-9666.

Matsumura, Shigeyoshi, et al. "Transient compartmentalization of RNA replicators prevents extinction due to parasites." Science 354.6317 (2016): 1293-1296.

Requirements

We are seeking a highly motivated Post-Doc with strong experience in molecular biology (PCR, qPCR), RNA, biochemistry or directed evolution. Experience in microfluidics and bioinformatics are very appreciated.

Flexibility, autonomy, the ability to work in a highly multidisciplinary team and good interpersonal skills are essential.

Recruitment terms :
Starting date : December 2024
Duration : 1 year with renewal possibility

Salary : according to professional experience