Muscle and skin have the same genes: why are they so different?

$648
Raised of $10,000 Goal
7%
Ended on 3/27/14
Campaign Ended
  • $648
    pledged
  • 7%
    funded
  • Finished
    on 3/27/14

About This Project

DNA directs cells to make the right proteins to be a muscle cell, a skin cell, or other cell. In different cell types, DNA is modified (DNA methylation) to give the correct directions. This process is hijacked in cancer, as shown in our pioneering research.
We use powerful new tools to understand novel ways that DNA accomplishes this directorial role in human development, which is critical for tackling the misdirection of DNA in cancer cells.

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What is the context of this research?

Our body is built up of pin-prick sized
units called cells. Genes (on DNA molecules) direct all the activity of our cells, tissues and organs. There are slight differences in genes between different individuals, and so we all don’t look alike. However, in one person, almost all the trillions of cells have identical genes because they arise from a single fused egg and sperm.

So how is it that a muscle cell in our biceps looks and behaves utterly differently from a skin cell? This involves turning on different collections of genes. How does this happen?

With breakthrough methods for determining the sequence of the 3 billion building blocks in DNA per human cell, we are learning the different placement of little chemical tags (DNA methylation) on genes in different types of cells and tissues. DNA methylation is part of "epigenetics," one of the most exciting areas of science.

Viva la differences in DNA methylation that are a major reason that different tissues look and behave dramatically differently!

I and my mathematician co-investigator, Michelle Lacey, use biostatistics to analyze the patterns of millions of DNA methylation data points in 31 different human tissues or cell types. Focusing on muscle, we discovered evidence for new roles for DNA methylation in establishing cell identity and function.

Now, we are ready to do some experiments to directly test our hypothesis that these tags are directing gene function in a muscle-specific way.

What is the significance of this project?

Normal muscle function depends on repairing muscle damage including
wear-and-tear of everyday life. With age, our muscles get weaker and are less efficiently repaired. In muscular dystrophy patients, this repair often is highly defective, leading to disease.

Understanding how chemical tags on genes allow muscle cells to behave properly and participate in muscle repair could lead to treatments to improve muscle repair and decrease muscle loss due to aging or disease.

In addition, cancers almost always have changes in DNA methylation. Muscle genes, including ones we will study, are surprisingly often targets for these changes, which may help the cancer progress or just serve as valuable markers for cancer detection.

What are the goals of the project?

We will test our hypothesis that naturally occurring chemical tags on genes (DNA methylation) are important in novel ways for directing muscle formation and repair. Using biostatistics, we will choose the most relevant DNA fragments to clone and introduce into muscle or skin cells growing in culture plates. These cells are cryopreserved in my lab. We will test the effect of putting the muscle-specific gene tags (DNA methylation) on them before introduction into the cells.

The requested funds will be used to purchase materials needed to grow the cells, introduce cloned DNA into them with or without muscle-type DNA methylation patterns, and test the functional effects of this DNA methylation.

This will pave the way for more research on these very little studied muscle-specific gene tags and their role in muscle formation and repair as well as in cancer.

Budget

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We are seeking $10,000 for this project. We already have the muscle and skin cells we will be using but will need supplies to grow the cells in the lab. Secondly, we need supplies to clone DNA fragments that will be introduced into the cells and to add DNA methylation to the DNA. Lastly, we will need to test the biological behavior of the cells (both with and without the added DNA methylation), and this too requires supplies.

Meet the Team

Melanie Ehrlich
Melanie Ehrlich
Michelle Lacey
Michelle Lacey

Team Bio

In collaboration with Charles Gehrke at the Univ. of Missouri, Columbia, we were the first to demonstrate different amounts of DNA methylation in different human tissues. DNA methylation is the only natural chemical modification of human genes.
We also pioneered research on DNA methylation in cancer.

Recently I have been collaborating with Michelle Lacey, Assoc. Prof. of Mathematics at Tulane University, to study muscle-specific differences in the patterns of DNA methylation. We compared 1 million DNA sites that are natural targets for this modification in 31 different human tissues or cell cultures. We published three papers in 2013 about some of the important genes with remarkable muscle-specific DNA methylation patterns.

We also just published a paper about statistical methods to analyze huge amounts of DNA methylation data.

We have not yet tested our hypotheses about how unusual patterns of muscle-specific DNA methylation influence gene expression. That is the core of this proposal.

Michelle Lacey

I'm an Associate Professor of Mathematics at Tulane University. My training is in Statistics (PhD, Yale 2003) and I have an adjunct appointment in the Department of Biostatistics and Bioinformatics at the Tulane University School of Public Health and Tropical Medicine. I'm a member of the Tulane Cancer Center and very much enjoy my collaborations with biomedical researchers. My primary research interests are in phylogenetics (estimation of evolutionary trees from molecular data), epigenetic modeling and analysis, and the development of statistical methods for the integration of biological data from a variety of sources.

Lab Notes

Nothing posted yet.

Additional Information

Here's some more explanation of our project and the figures shown in the video.










Banner image:

Skeletal muscle cells from quadriceps are shown in the process of fusing to form microfibers (myotubes). The green color is a fluorescent dye staining a muscle-specific protein that lights up the cell. The blue circles are the nuclei where the DNA and its genes are located. The pink arrows point to many nuclei in one long cell that are arranged like peas in a pod after cell fusion. Bundles of these myotubes contract and relax to make our arms and legs move. Almost all other cell types in our body boringly have just one nucleus per cell.


Here is an example of a gene with a muscle-specific DNA methylation pattern:







To see one of our recent publications with muscle-specific DNA methylation data, click here.



Project Backers

  • 9Backers
  • 7%Funded
  • $648Total Donations
  • $72.00Average Donation
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