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Cardiology Research Groups

Srinivas Group

Research Aims & Objectives

Our broad aim is to understand at the cellular and genetic level how embryonic pattern is specified. Specifically, we focus on:

  • how the coordinated cell movements that shape the early mammalian embryo prior to and during gastrulation are controlled
  • how the embryonic heart forms and starts to beat

Details of research interests

Large-scale cell and tissue movements play a major role in shaping the mammalian embryo. For instance, the embryonic region that gives rise to the heart actually starts out in front of the region that forms the brain. Little is currently known about how the movement of cells within tissues such as epithelia is coordinated to give the intricately shaped structure of the body and the genetic control of these complicated movements. We take a multidisciplinary and collaborative approach to address these questions in mouse and human embryos, using techniques spanning molecular genetics, lightsheet and confocal time-lapse imaging, machine learning, single cell approaches, proteomics and embryo explant culture. 

In order to understand how anterior-posterior axial asymmetry is specified, we study the stereotypic movement of the Anterior Visceral Endoderm (AVE) that is responsible for establishing this asymmetry. We look at the cellular and molecular control of AVE migration, as well as how coordinated behaviour of individual cells within an epithelial sheet results in large scale morphogenetic remodelling. We study how the AVE defines the site of formation of primitive streak and controls the cell movements that accompany gastrulation. As part of a Wellcome funded collaboration, we also study how cellular diversity is generated during gastrulation.

The heart is the first organ to form and function during mammalian embryogenesis. It is composed of not only cardiomyocytes but also a variety of other cell types essential to its function. The heart is unusual in having to contract rhythmically whilst still undergoing extensive morphogenetic remodelling. Thus, the development of form and function of the embryonic heart are inextricably linked. We study how the mesoderm formed during gastrulation goes on to generate the diverse cell types of the heart, the genetic basis for its left-right asymmetric development and how the synchronous calcium oscillations essential for triggering rhythmic contractions in the embryonic heart are established. We are also part of the Wellcome-funded Human Developmental Biology Initiative (HDBI) which seeks to gain fundamental insights into human development.  Our focus is on establishing the cell lineages contributing to the embryonic human heart and characterising key morphogenetic events, such as outflow tract formation and septation of the chambers, that are implicated in congenital heart disease.
 

Group Leader

Shankar Srinivas

Group Members

  • Jonathan Godwin 
  • Dr Matthew Stower
  • Dr Shifaan Thowfeequ
  • Dr Tomoko Watanabe

Collaborators

Collaborators - External:

  • John Marioni (University of Cambridge)
  • Wolf Reik (Babraham Institute, Cambridge)
  • Tristan Rodriguez (Imperial College London)
  • Antonio Scialdone (Helmholtz Zentrum München)
  • Irene Yan (University of  São Paulo)

Funders

  • Wellcome Trust
  • Medical Research Council

Public Engagement

We participate actively in outreach, through stalls in science festivals, visits to schools, radio interviews, and public lectures. We incorporate our research data into our outreach material, for example using our high-resolution confocal image volumes of research samples to print 3D models of embryonic hearts that members of the public can handle. We have also developed a Virtual Reality based embryo and microscopy image explorer to provide the public with an immersive experience of developing embryos. In addition to outreach, we are also active in public engagement activities where we work closely with non-scientists over a longer term to achieve mutual insights. For example, we collaborated with the Parasol Dance Group on a project where young dancers used our time-lapse movies of heart development as inspiration for their dance moves. 

Shaping Destiny: Experiments in Embodiment

Shaping Destiny logo.png

Shaping Destiny is a multi-disciplinary public engagement project led by members of the Department of Physiology, Anatomy and Genetics (DPAG) and TORCH. We are bringing together the fields of molecular biology and the arts, to explore the concepts of ‘destiny’ and ‘embodiment’. The science side, led by Professor Shankar Srinivas of the Srinivas Group, wrestles with the concept of ‘determinism’ and how certain cells are destined to create the certain body parts to which they relate (for example, heart cells are destined to form a heart). However, there are limits to the role of genes – through the project, we will investigate how our external environments and social norms influence our destiny and embodiment. On the humanities side, Professor Wes Williams, Director of TORCH, is exploring the idea of the human ‘norm’. Wes will delve into the perception of human differences through history. In the past, society explained congenital defects to be the work of devilish or divine intervention, or by the actions or thoughts of the mother during pregnancy. Dr Tomoko Watanabe, a scientist in the Srinivas group, is the project lead, coordinating the activities with the academic and non-academic project partners.

Shaping Destiny will work alongside external partners and community groups to explore these concepts via dance, theatre, and virtual reality. We will provide a cross-departmental study into embodiment and destiny which will provide us with an understanding of the link between the biological formation of organs and tissues and the development of human beings through social norms.

The team will be looking for volunteers to help at a number of stages across the project. Expressions of interest can be sent to Project Lead Dr Tomoko Watanabe.

Read more on the Shaping Destiny project webpage (TORCH website)

 

Recent Publications

Publications Directory

Contact Information

shankar.srinivas(at)dpag.ox.ac.uk