School of Biosciences
 

Image of Ramiro Alberio

Ramiro Alberio

Professor of Developmental Biology, Faculty of Science

Contact

  • workRoom Room B234 South Lab
    Sutton Bonington Campus
    Sutton Bonington
    Leicestershire
    LE12 5RD
    UK
  • work0115 951 6304
  • fax0115 951 6099

Biography

I obtained my undergraduate degree in veterinary medicine from the University of La Plata, Argentina in 1996 and earned a PhD (Suma Cum Laude) from the University of Munich, Germany in 2001. My first postdoctoral training was done under supervision of Prof. Keith Campbell (2001-2003). In 2002 I was awarded a Marie Curie Fellowship (2002-2004) followed by an RCUK Fellowship (2005-2010). In 2010 I took up a position as Lecturer and was later promoted to Associate Professor (2015) and to Professor of Developmental Biology (2019) at the Division of Animal Sciences, School of Biosciences, UoN.

Expertise Summary

Our laboratory studies how cells become specialized during the formation of the fetus. We have special interest in the development of the precursors of the gametes, sperm and egg. We have used the pig embryo as a model system for understanding processes shared with human embryos. We have identified a key molecular program, based on the activation of the gene SOX17, in the precursors of the germ line. We have also identified sets of genes that escape DNA demethylation that are shared with those found in the human germline. These loci have the potential to carry epigenetic information across generations. The mechanisms underlying these processes are of considerable interest for understanding the basis of transgenerational inheritance.

For gaining detailed understanding of these events our laboratory uses molecular techniques that include single cell transcriptomics and bioinformatics. We also perform genome wide epigenetic analysis using PBAT and ATAC seq. We combine high-throughput technologies with gene editing using CRISPR/Cas9 systems to perform functional investigation in in vitro differentiation models as well as embryo editing.

We also have interest in understanding the molecular regulation of stemness in domestic animal embryos. We have used single cell sequencing techniques to define the molecular program of early pig embryos ans used this knowledge to derive embryonic stem cells and propagate them long term. These cells can give rise to all cell lineages. We have focussed in the derivation of muscle and fat progenitors with the aim of generating muscle in vitro. The purpose of this platform is to enhance the differentiation of these cells towards lab-grown meat, but also contribute to generating models of muscle for functional analysis of specific gene loci with high breeding value.

Teaching Summary

Biotechnology in Animal Physiology (BIOS3005; Module convenor)

Animal Biotechnology (BIOS4122, module convenor)

Regulation and Organisation in Animals (BIOS2088)

M.Med Sci in Assisted Reproductive Technology (A117)

Research Summary

Our laboratory investigates the developmental mechanisms of early mammalian embryos. Our aim is to gain understanding of the molecular regulation of cell decisions during the onset of gastrulation.… read more

Selected Publications

Current Research

Our laboratory investigates the developmental mechanisms of early mammalian embryos. Our aim is to gain understanding of the molecular regulation of cell decisions during the onset of gastrulation. This is the period when the key lineages that make the adult organism are first set in the fetus. Understanding how these processes are controlled in vivo can help us develop better technologies for the generation of useful cell types in vitro and with potential uses in regenerative medicine and livestock production.

Our lab is embedded within CeLAB (https://www.nottingham.ac.uk/research/groups/large-animal-biotechnology/), a unique UK resource dedicated to research in Large Animal Biotechnology.

The current main research areas in our lab include:

Germ cell development in mammals

Germ cells are responsible for passing the genetic information of the parents to the next generation. The developmental program of these cells involves unique mechanisms that erase epigenetic memory (or epimutations) that may otherwise be passed on to the next generation. Our laboratory has shown that the germ cells in human and pig embryos are specified via similar mechanisms, thus making investigations in pig embryos of relevance to understanding human development (Kobayashi et al., Nature 416: 426-30, 2017; Zhu et al., Cell Reports 34:108735, 2021). Large mammals (humans, pigs, sheep and cows) have slower development, suggesting that the mechanisms for the establishment of different cell lineages, including the germline, may be under different control than those of mice. An important difference between the embryos of mice and other mammalian species, is that mouse embryos develop as a conical structure, which implies that cellular movements are very characteristic for this type of embryo. Other mammals develop as a flat embryonic disc, which means that the cellular movements are completely different to rodents. Given that many aspects of early pig embryo development are similar to human embryos, we use these embryos to uncover fundamental mechanisms of germ line development with relevance to human. The findings from our in vivo characterization are validated with functional experiments using human ESC/iPS and pig EpiSC/iPS. We anticipate that this work will help us develop efficient methods for generating gametes in the laboratory, which will be useful for understanding the basis of infertility, but also with important applications in animal biotechnology.

Mechanisms of gastrulation in mammals

During the first three weeks of development the human fetus becomes almost completely formed. Hitherto, most of our understanding of development is inferred from mouse studies, because human embryos cannot be studied after they implant around of day 9 after fertilization. The pig has recently emerged as a valuable model species that can inform on fundamental mechanisms of human development, is easily accessible and is important in biomedical research. Given that fundamental questions about cell lineage decisions during early gastrulation, also known as the black box of development, remain unanswered, and are critically important for understanding the basis of early embryo mortality and birth defects, we have focussed our efforts in gaining new understanding of pig developmental biology. Our laboratory has made fundamental discoveries showing that pig embryos can be used to broaden the knowledge of human development (Ramos-Ibeas et al., Nature Communications 10:500, 2019), and represent an accessible and ethically acceptable source of embryos for research. Furthermore, given that the pig is an excellent model for biomedical research, increasing our knowledge of its developmental biology will have an impact in human regenerative medicine and our understanding of human genetic diseases.

Stem Cell Technologies in livestock species

We have gained detailed understanding of the developmental trajectories of cells that constitute de pre-implantation pig embryo using single cell genomics (Ramos-Ibeas et al., Nature Communications 10:500, 2019). With this knowledge we have develop novel methods for derivation of embryonic stem cells from diverse domestic animal embryos. These cells can be established easily and can differentiate into all cell lineages upon specific cues. We are using these new resource for diverse applications, including direct differentiation into specific lineages (such as muscle and fat to generate lab grown meat), as well as for the generation of in vitro gametes.

We are are using these cells for the study of gastrulation using in vitro gastruloids, an alternative model for functional investigation of gene function during development. This new resource will facilitate high-throughput investigations into fundamental questions of embryo development.

Funding

BBSRC, Medical Research Council, Wellcome Trust.

Current Lab Members:

Dr. Andrew Strange (Research Fellow)

Doris Klisch (Lab Manager)

Sophie Kraunsoe (Research Associate)

Jess Wong (MRes student)

Zachary Muda (PhD student)

Eva Simpson (PhD Student)

Gizem Guven (PhD student)

Luke Simpson (PhD student)

Imge Duru Onol (PhD student)

Former Members:

Sebastian Lazar, MPhil (2008)

Xiaoni Sun, MRes (2010)

Alejandro Contreras, PhD (2011), now Senior scientist at University of Mexico

Somsin Petyim, PhD (2013), now Head of Obs & Gynaecology, Bangkok, Thailand.

Griselda Valdez Magana, PhD (2014), now Senior scientist at University of Mexico

Sergio German, PhD (2015)

Dr. Adam Hirst (Postdoc) now Senior Scientist at Stem Cell Technologies, Vancouver, Canada.

Haixin Zhang, PhD (2016), now postdoc at University of Cambridge.

Sidar Bereketoglu, PhD (2016), now group Leader at university of Ankara, Turkey.

Choulia Mola, PhD (2017)

Fabio Amaral, PhD (2017)

Darren Crowley, PhD (2018), now senior scientist at Ely Lilly, Ireland.

Haitham Alhilfi, PhD (2018), now academic in Irak.

Judith Gomez-Martinez, PhD (2018), now human embryologist at IVF clinic.

Liam Wood, MRes (2018)

Dr. Priscila Ramos-Ibeas (Postdoc), now group Leader at INIA Madrid, Spain

Dr. Sarah Withey (Postdoc), now Research Fellow, at University of Brisbane, Australia.

Qifan Zhu, PhD (2021), now Postdoc at CEMC, CAS, Shanghai, China.

Future Research

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School of Biosciences

University of Nottingham
Sutton Bonington Campus
Nr Loughborough
LE12 5RD, UK

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