University of Manchester and St Mary’s Hospital
This project involves studying early human embryo development. The researchers want to find out what factors contribute to normal embryo development, and what happens when development goes wrong. They will be assessing the impact of sperm DNA damage and factors which might affect embryo development and implantation into the womb, including the culture environment and the effect of freezing embryos.
It is necessary to use human embryos for this research as although important information has come from studies of animal embryos, they develop differently to human embryos.
Wellcome Trust Centre for Stem Cell Research University of Cambridge
Embryonic stem (ES) cells were first identified in mouse embryos in 1981. Cells similar to ES cells can be made by manipulating differentiated cells (for example skin or nerve cells) to make ‘induced pluripotent cells’ (iPS) cells.
ES and iPS cells have the unique ability to turn into any tissue in the body. ES and iPS cells can now also be obtained from human embryos and adult tissues. However, human stem cells are not as consistent and reliable as mouse stem cells. In this project, human and mouse embryos are compared with the aim of developing ways to improve human ES cells so that they’re easier to grow and can differentiate into wider range of tissues.
Mitochondria are small structures found in cells and are essential for cells to function. An important part of their activity is to produce the cell’s energy. Mitochondria contain DNA called mitochondrial DNA. Different cells contain different amounts of mitochondria depending on the size of the cell and its energy needs. Egg cells contain a high number of mitochondria.
Embryos inherit mitochondria and mitochondrial DNA exclusively from the egg cell. This project is looking at how mitochondrial DNA is distributed in the early embryo and if their number is related to chromosomal abnormalities.
The Francis Crick Institute at Mill Hill
This research is concerned with early human embryo development. It is hoped that the results of these studies will benefit medical knowledge in a number of important ways.
Firstly, by improving understanding of the conditions that are important for growing human preimplantation embryos in a petri dish. These insights can hopefully lead to improvements in the treatment of infertility.
Secondly, by improving our understanding of how early human embryo cells become more specialised during early development. The first critical step in this process is when a small subset of cells are set aside to eventually form the foetus, whilst another subset of early cells differ in their fate to become the placenta (which supports the development of the foetus throughout the pregnancy). We are interested in how these specialisation events occur and are regulated before implantation. Understanding the genes that are essential for this first important specialisation process could provide insight into some causes of pregnancy failures and birth defects. Understanding this important switch in cell fate may also provide a deeper understanding of stem cell formation.
Lastly by developing stem cell lines that can be taken out of the embryo and multiplied in the laboratory for many years. This can help to study and better understand devastating human diseases at the cellular level in the laboratory and potentially develop new drug treatments.
The Gurdon Institute, University of Cambridge
A high proportion of natural abortions occur because of developmental failure as the embryo implants into womb. To avoid such failures in the IVF clinic, it would be helpful to know what an embryo must achieve during the initial days when it is placed in the mother’s womb. This project involves culturing embryos in an in vitro (artificial) environment that has been shown to permit the correct development of an embryo until day 13.
For the first-time this allows researchers to study human embryo development from day 7 to day 13, a period that normally cannot be seen. This research will help in understanding the causes underlying early pregnancy loss.
Cardiff University School of Biosciences
At fertilisation, the sperm fuses with the egg and sends a calcium signal to trigger it to begin development. Without this signal, the process of fertilisation is not successful and an embryo cannot be made. In a proportion of IVF and ICSI treatments it appears that the egg fails to fertilise because of a lack of this activating calcium signal.
Previous research in mouse eggs has shown that sperm contain a protein, referred to as PLCzeta, which enters the egg during fusion and triggers the calcium changes that lead to egg activation and embryo development. We now want to extend some of these studies to human eggs.
In this project, human eggs that have failed to fertilise during IVF treatment cycles will be injected with the PLCzeta protein to see how effective it is in stimulating the calcium changes that cause egg activation. We will compare the effectiveness of PLCzeta protein with certain chemicals that have been used by some clinics to stimulate calcium changes in human eggs that have failed to activate after ICSI treatment.
This work could provide important information on how the sperm normally triggers development during human fertilisation. It may help explain why some eggs fail to fertilise after procedures such as ICSI, and it would offer new ways to overcome such fertilisation failure.
Guys Hospital, London
This project is testing a technique involving the splitting of embryos. If successful, it could be possible to split one embryo into two, both of which will have the same genetic information. Embryos for research can be hard to obtain so by being able to split one, it reduces the number of embryos used and avoids genetic background bias.
At fertilisation, the sperm activates the egg to begin development in a process called egg activation. A protein called PLCzeta is important in this process. If there is not adequate PLCzeta then the egg may not be successfully fertilised. Men without adequate PLCzeta may therefore be infertile. This project involves using a synthetic version of PLCzeta created in a lab and seeing if it can be used for fertilsation where there are low levels of natural PLCzeta.
The second part of this project involves using high-frequency time lapse filing to observe the tiny movements that take place in an egg during the first few hours after activation. These, and other experiments on eggs and very early stage embryos, will increase our knowledge of the processes that occur around fertilisation. In the future, the synthetic PLCzeta could be used to help in cases where there are egg activation problems, and use the time lapse technique to predict which embryos are healthier for transfer in IVF.