Transcriptional Basis of Non-Genetic Cellular Heterogeneity – Vicent Pelechano group

Genomic dissection of non-genetic cellular heterogeneity

In the last decades, the biomedical field has suffered a revolution thanks to the development of the massive parallel sequencing technologies. Now we can obtain the complete genetic information of a person and analyse how this information is being used in a few days and with a limited cost. This technology makes possible a kind of research that was unthinkable a few years back. Our group, combining experimental and computational work, aims to develop and apply novel genome-wide techniques to address fundamental biological questions with medical implications. We are especially interested in how subtle variations in gene expression can lead to differential cellular phenotypes in humans and microorganism.

Specifically, we investigate:

1. Molecular bases of non-genetic cellular heterogeneity: We focus on understanding how single-cell variability, cellular plasticity and transcriptional memory contribute to the appearance of drug-tolerant cancer persister cells (i.e. those cells that, although genetically sensitive to a drug, do not respond to it). To reach that goal we combine the dissection of genetic factors controlling non-genetic heterogeneity with the development of novel genome-wide technologies to study this process.
2. Crosstalk between ribosome dynamics and mRNA degradation. We have previously shown how the existence of widespread co-translational mRNA degradation allows to study ribosome dynamics by sequencing mRNA degradation intermediates (5P-Seq). Using that work as staring point, we to dissect the molecular crosstalk between mRNA degradation and ribosome dynamics in multiple organisms. We are characterizing how alterations in the translation process modulates mRNA stability and explore the utility of mRNA degradation signatures as reporters for cellular fitness in multiple organisms (from bacteria to cancer cells). 
3. Novel tools for molecular diagnosis. We are using our genomics expertise to improve and develop new molecular diagnosis and clinical genomic tools. We develop sequencing-based approaches to improve cancer-patient stratification and to accelerate the diagnosis of antimicrobial resistant infections.

Alumni

2021

• Dr. Bingnan Li. Postdoc (2016-2021)
• Gijs van Riel. Research Technician. (2020-2021)
• Femke van Hout. Erasmus+ student. University of Nijmegen (Netherlands)
• Benjamin Maier. Summer intern from the SciLifeLab Master’s programme in Molecular Techniques in Life Science.h Technician. (2020-2021)

2020

• Dr. Jingwen Wang. Computational Postdoc (2017-2020)
• Fiona Roß. Research internship part of the Master Program in Biomedicine at Karolinska Institutet.
• Maria Ropat. Research Assistant in Bioinformatics

2019

• David Andreu Sanz. European Amgen Scholars Program at Karolinska Institutet.
• Yuanyuan Xi. Master project for the SciLifeLab Master’s programme in Molecular Techniques in Life Science.
• Maria Ropat. Master project for the SciLifeLab Master’s programme in Molecular Techniques in Life Science.
• Laura de Lara Peña. Erasmus+ student. University of Sevilla (Spain)
• Cristina Mérida Mena. Erasmus+ student. University of Jaen (Spain)

2018

• Maryia Ropat. Summer research project for Master students. Master’s programme in Molecular Techniques in Life Science.
• Inka Schröter. Erasmus+ student. Technical University of Darmstadt (Germany)

2017

• Maryia Ropat. Summer research project for biomedical students. Karolinska Institutet.
• Abel Cuevas Bermudez. Visiting PhD student. Universidad de Jaen (Spain)

2016

•  Yerma Pareja Sanchez. Erasmus+ student. University of Seville (Spain)

We always welcome applications from motivated postdoctoral researcher, PhD student, or Master students.

Applicants for post-doctoral positions

Experience with genetics, molecular biology and/or bioinformatics are required.

Applicants wishing to integrate computational and experimental biology approaches are especially encouraged to apply.

Current projects focus on the understanding of the gene expression programmes underpinning phenotypic heterogeneity within clonal populations and on how to use that information to refine our knowledge of the basic process of gene expression. To reach that objective we develop and apply novel genome-wide approaches in budding yeast and human cell lines.

The successful candidate is expected to take a strong lead on his/her project and start to develop independent ideas.

For applications, please contact Vicent Pelechano by email and attach your CV and a brief motivation letter with your research interests.

Applicants for PhD positions or Master students

Students will have the opportunity to learn and help develop a variety of experimental and bioinformatic tools.

A theoretical background and / or interest in either functional genomics, transcription, or bioinformatics is beneficial. Students are expected to be highly motivated to work on challenging research projects in an international team.

For applications, please send your CV and a brief motivation letter to Vicent Pelechano.