Plass Group

gene regulation of cell identity
Alternative polyadenylation and other post-transcriptional regulatory processes are key mechanisms responsible to define the transcript repertoire of cells. Using a combination of high-throughput sequencing and computational approaches, we study how these mechanisms influence cellular differentiation and their contribution to the development of neurodegenerative diseases.
Mireya Plass
Group Leader, Regenerative Medicine Program of IDIBELL
Group Leader of P-CMRC

Lab focus – Understanding post-transcriptional regulation in cell differentiation and its alteration in neurodegenerative diseases

The mechanisms that define cell identity in complex organisms are still largely unknown. Most efforts have been focused on understanding how a few transcription factors direct cell differentiation in particular circumstances, such as during development or in cancer. However, many post-transcriptional processes, which are essential for defining the final transcript repertoire in a cell, have been overlooked and their role in establishing this identity is much less understood. In the lab, we want to understand how post-transcriptional regulatory processes, and in particular alternative polyadenylation, are coordinated at the individual cell level and how they contribute to the differentiation of cells both in health and disease conditions.

By combining single-cell transcriptomics with cellular reprogramming we can characterize at the molecular level how gene expression and post-transcriptional regulation are altered in several conditions and which is their contribution to the development if neurodegenerative diseases. By differentiating iPSCs to different types of neurons and other neural related cells, we can now study the differentiation process globally and identify all the gene expression changes responsible for the differentiation of individual cell types. Additionally, by comparing the differences in the differentiation of patient-derived and healthy iPSCs cells, we can identify the altered gene pathways that explain the onset and the progression of the disease.

Why it matters

The molecular mechanisms responsible for the development of neurodegenerative diseases, such as Alzheimer’s and Parkinson’s disease, are still largely unknown. We want to investigate how the basic molecular biology mechanisms involved in the regulation of RNA are altered in neurodegenerative diseases. This research will likely contribute to identify new targets for the development of new diagnostic tools and personalized medicine interventions.

Keywords

Single-cell transcriptomics, post-transcriptional regulation, alternative polyadenylation, neural differentiation, computational biology, neurodegeneration

Publications

Plass M*, Solana J*, Wolf FA, Ayoub S, Misios A, Glažar P, Obermayer B, Theis FJ, Kocks C, Rajewsky N. Cell type atlas and lineage tree of a whole complex animal by single-cell transcriptomics. Science. 2018 May 25;360(6391). pii: eaaq1723. doi: 10.1126/science.aaq1723. Epub 2018 Apr 19. PubMed PMID: 29674432. *authors contributed equally to this work.
Plass M*†, Rasmussen SH*, Krogh A†. Highly accessible AU-rich regions in 3′ untranslated regions are hotspots for binding of regulatory factors. PLoS Comput Biol. 2017 Apr 14;13(4):e1005460. doi: 10.1371/journal.pcbi.1005460. eCollection 2017 Apr. PubMed PMID: 28410363; PubMed Central PMCID: PMC5409497. *authors contributed equally to this work. † co-corresponding authors.
Rehfeld A*, Plass M*, Døssing K, Knigge U, Kjær A, Krogh A, Friis-Hansen L. Alternative polyadenylation of tumor suppressor genes in small intestinal neuroendocrine tumors. Front Endocrinol (Lausanne). 2014 Apr 15;5:46. doi: 10.3389/fendo.2014.00046. eCollection 2014. PubMed PMID: 24782827; PubMed Central PMCID: PMC3995063. *authors contributed equally to this work.
Plass M, Eyras E. Approaches to link RNA secondary structures with splicing regulation. Methods Mol Biol. 2014;1126:341-56. doi:10.1007/978-1-62703-980-2_25. PubMed PMID: 24549676.
Macias S, Plass M, Stajuda A, Michlewski G, Eyras E, Cáceres JF. DGCR8 HITS-CLIP reveals novel functions for the Microprocessor. Nat Struct Mol Biol. 2012 Aug;19(8):760-6. doi: 10.1038/nsmb.2344. Epub 2012 Jul 15. PubMed PMID: 22796965; PubMed Central PMCID: PMC3442229.
Plass M, Codony-Servat C, Ferreira PG, Vilardell J, Eyras E. RNA secondary structure mediates alternative 3’ss selection in Saccharomyces cerevisiae. RNA. 2012 Jun;18(6):1103-15. doi: 10.1261/rna.030767.111. Epub 2012 Apr 26. PubMed PMID: 22539526; PubMed Central PMCID: PMC3358634.
Current Members
Current Members
ANA GUTIÉRREZ FRANCO
Research Assistant
Franz-Arnold Ake
PhD student

Mireya Plass
Group Leader, Regenerative Medicine Program of IDIBELL
Group Leader of P-CMRC

mplass@idibell.cat

Dr. Mireya Plass studied a BS in Biology (2005) and holds a PhD in Health and Life Sciences (2011) from Pompeu Fabra University (Barcelona, Spain). She pursued postdoctoral training abroad first at the University of Copenhagen (Krogh Lab, 2011-2015) and later at the Berlin Institute for Medical Systems Biology (N. Rajewsky Lab, 2016-2019) before returning to Spain to complete her post-doctoral training at the Center for Genomic Regulation with a Marie Sklodowska-Curie Fellowship (Irimia Lab, 2019). In October 2019, she joined the CMRB as independent group leader.

Throughout her career, Dr. Plass has been interested in understanding how post-transcriptional regulatory mechanisms, such as splicing and alternative polyadenylation, shape gene expression from an evolutionary and systems biology perspective. Recently, her work has pioneered the use of single-cell transcriptomics to understand how gene expression drives cellular differentiation. As independent group leader, she wants to investigate the function of post-transcriptional regulation in gene expression and cell differentiation, and in particular its contribution to the development of neurodevelopmental and neurodegenerative diseases.

ANA GUTIÉRREZ FRANCO
Research Assistant
agutierrezf@idibell.cat

Dr. Ana Gutiérrez Franco holds a BSc in Biotechnology by Universitat Autònoma de Barcelona (2010) and MS in Neuroscience (2011). During her PhD at Vall d’Hebron Research Institute (Dr. Carmen Espejo and Dr. Xavier Montalbán, 2010-2014) she studied the role of Semaphorin 3A and 7A in the neuroregulation and immunomodulation in multiple sclerosis. She performed a short stay of three months at the Center of Clinical Brain Sciences at the University of Edinburgh to study the role of TNF-alpha in iPSC cells derived from ALS patients and differentiated to oligodendrocytes.

Her first postdoc at Institute Germans Trias i Pujol was focused on the evaluation of experimental treatments in a mouse model of Sanfilippo syndrome targeting autophagy mechanisms (Dr. A. Matilla, 2015). After that, she joined the Evolutionary Genomic lab led by Prof. Fyodor Kondrashov at the Center of Genomic Regulation as a post-doctoral scientist to study the potential compensatory mechanism of Lamp2A over a Parkinson’s disease causative mutation in alpha-synuclein (2016). In 2017, the group moved to the Institute of Science and Technology in Vienna. There, she combined her research on alpha-synuclein and Lamp2A interaction, with managerial duties as she was in charge of the experimental lab and supervision of students and technicians.

During these years she has acquired expertise in cell culture techniques and neurodegenerative mice model handling and deep knowledge of immunomodulation, autophagy, and neurodegeneration.

For the past three years, she has also been the Lab Manager of an annual summer school program (School of Molecular and Theoretical Biology) that merges real science projects with highly motivated and talented high school students from around the world.

She joined the P-CMR[C] in June of 2020 as a Research Assistant in Mireya Plass’ group to study the influence of alternative polyadenylation in neuronal differentiation and the development of neurodegenerative diseases.

Franz-Arnold AKE
PhD student
fake@idibell.cat

Franz obtained his BSc (2016) in Biology (Biology/Biochemistry – option Bioinformatics) and a MSc in Bioinformatics (2019), realised at University of PARIS – Sorbonne Cité USPC,  where he got during his formation, courses and skills in several Bioinformatics areas (mainly Structural, Omics, Stats & Programming).

As part of his MSc courses, he got the opportunity to realise several internships. First, in the National Center of Scientific Research (CNRS) Lab in Paris, with the team Post-transcriptional and Epigenetic regulation (PTER) about the implementation of unsupervised Machine Learning approaches for selection of co-translated mRNAs under the supervision of Prof C. BOUYIOKOS, and after, a second internship at the Hydraulic & Environmental National Laboratory Department (LNHE – Electricite de France EDF) in Paris about Legionella Pneumophila biotics and abiotics interaction and proliferation problematics inside Nuclear cooling Circuit.

After the end of his academical course, he worked mainly on Metagenomics applications. Firstly, he worked in the same group as his last internship as bioinformatic engineer on L. Pneumophila problematic (EDF-Lab / LNHE). Secondly, he worked as a computational biologist at the National Research Institute INRAe-Transfert (INRAE) based in the sequencing genetic platform GET in Toulouse, about post-sequencing bioinformatic and biostatistical data analyses.

Franz joined the Dr Mireya PLASS’ group for his PhD on Single-cell transcriptomic analyses for understanding RBPs contribution to cell differentiation, and how the transcriptomic networks regulated by these RBPs are altered in the development of neurodegenerative disease.