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Karam Teixeira Group

Molecular Mechanisms Controlling Germline Stem Cell Biology

Research Interests

We focus on the development of the germline, the ‘immortal’ cell lineage that provides the continuity of life and ensures the transmission of genetic information through generations. In particular, we are interested in the genetic and molecular mechanisms controlling germline stem cell behavior and protecting totipotency in vivo.

Gene expression regulation during stem cell self-renewal and differentiation

Germ cells are considered to be the ultimate stem cell lineage as they are competent not only to generate more germ cells but also to give rise to a new organism every generation. Not surprising, the study of the germline has been instrumental for the understanding of the mechanisms of pluripotency and stem cell biology, with broad implications to regenerative medicine, aging, and cancer. Our lab uses the Drosophila ovary as a model for studying germline stem cell biology because this system is amenable to detailed developmental analysis as well as for large-scale experimental approaches. Thanks to this, we were able to assemble the complete genetic framework controlling germline stem cell self-renewal and differentiation in vivo, revealing new aspects of germline development – including the translational control of stem cell cytokinesis, the uncoupling of ribosome biogenesis and protein synthesis rates during stem cell development, and an energy metabolism-independent function for mitochondria governing differentiation.

From plants to mammals, accumulating evidence indicate that regulation of protein synthesis plays critical roles during organism development, tissue homeostasis, and tumorigenesis. Yet, the study of spatiotemporal regulation of gene expression and its function in controlling stem cell biology has been mostly restricted to chromatin-based mechanisms. Nevertheless, gene expression analyses indicate that protein abundance in cells is mainly regulated at the translational level. Interestingly, translational regulation appears prominent in the germline, as no master transcription factor has been identified to specify germ cell fate. Using a combination of high-throughput molecular approaches, computational investigation, as well as developmental and genetic analyses, our goal is to dissect the molecular mechanisms by which protein synthesis control - a new frontier in gene regulation - governs key aspects of germline stem cell development in vivo.

Transposable elements and germline development

Repeat elements, such as transposable elements (TEs), make up about 30% and 50% of the Drosophila and human genomes, respectively. Since their discovery, TEs have been implicated in the organization, functioning, and evolution of genomes. However, TEs enhanced activity is detrimental to the host and therefore must be tightly regulated. This is especially true in the germline, where exacerbated TE activity can alter the inheritable genetic information.

A classic example of disruptive transposon activity is provided by hybrid dysgenesis in Drosophila, a syndrome that specifically affects germline development and is triggered by the P-element DNA transposon. In this system, the presence of epigenetically inherited small RNAs (sRNAs) cognate to the P-element correlates with germline protection, although the means by which this defense is achieved has remained elusive. Using this textbook example of genomic conflict and transgenerational epigenetics, our lab uses a combination of developmental and high-throughput molecular approaches to dissect the host-mechanisms controlling genome stability and transposon activity during germline development.

Selected publications

Sanchez CG*, Teixeira FK*#, Czech B, Preall JB, Zamparini AL, Seifert JRK, Malone CD, Hannon GJ, Lehmann R# (2016) Regulation of ribosome biogenesis and protein synthesis controls germline stem cell differentiation. Cell Stem Cell. 18:276-290. *Equally contributed. #Corresponding author.

Malone CD#, Lehmann R, Teixeira FK# (2015) The cellular basis of hybrid dysgenesis and Stellate regulation in Drosophila. Current Opinion in Genetics and Development. 34:88-94. #Corresponding author.

Teixeira FK*, Sanchez CG*, Hurd TR*, Seifert JRK, Czech B, Preall JB, Hannon GJ, Lehmann R (2015) ATP synthase promotes germ cell differentiation independent of oxidative phosphorylation. Nature Cell Biology. 17:689-696. *Equally contributed.

Teixeira FK (2011) The GE & Science Prize for Young Life Scientists 2011 - Mechanisms of Transgenerational DNA Methylation Inheritance.  Science. 334:1222-1223. http://www.sciencemag.org/site/feature/data/prizes/ge/2011/teixeira.xhtml

Teixeira FK, Heredia F, Sarazin A, Roudier F, Boccara M, Ciaudo C, Voinnet O, Cruaud C, Poulain J, Wincker P, Berdasco M, Fraga MF, Esteller M, Colot V (2009) A Role for RNAi in the selective correction of DNA methylation defects. Science. 323:1600-4.

Johannes F*, Porcher E*, Teixeira FK*, Saliba-Colombani V, Simon M, Agier N, Bulski A, Albuisson J, Heredia F, Audigier P, Bouchez D, Dillmann C, Guerche P, Hospital F, Colot V (2009) Assessing the impact of transgenerational epigenetic variation on complex traits. PLoS Genetics. 5:e1000530. *Equally contributed.

Page created 26 Sept 2017

Contact details

Group leader :
Dr Felipe Karam Teixeira

Address:
Department of Genetics,
University of Cambridge,
Downing Street,
Cambridge CB2 3EH,
United Kingdom

Email:
felipe.karam-teixeira@gen.cam.ac.uk

Tel.: +44 (0)1223 333957

Group members