The Sequenced Generation:
From your Inadequate Genome to your Dynamic Microbiome
Jonathan Lawson, Department of Biology
There is an understanding that genetic information has and will continue to
change science and medicine. We stand at a unique moment in history where our
technologies are enabling the collection of vast amounts of genetic data, while we
struggle to discover the knowledge encoded within it. Further distilling this
information into actionable knowledge for both human and environmental benefit
remains a promising and challenging pursuit. The possibilities seem infinite and
altruistic, but the paths to these goals are wrought with challenges on technological,
legal, and ethical fronts. What does seem clear is the sequencing technology is at
our doorstep. Presently, one can sequence his or her genome for the same cost as an
MRI or CT scan, and the cost continues to vector downward where the financial cost
of obtaining this information will no longer be prohibitory. Society will have a
knowledge and relationship with this information we are both hopeful for yet trepid
of developing.
I am seeking to explore three areas related to this topic through this study
grant proposal; the history and future of sequencing technologies, how the human
genome changed our perspective of ourselves through insights into diseases and
personalized medicine, and the interest and promises of our dynamic “second
genome”, the microbiome. These will be achieved through reading of published
books and primary scientific literature, as well as scientific commentary. As a
science educator I have found that many students do not see the role for biological
knowledge in their lives, or if they do, have little perspective on the personal
connections to this information. Engaging students to understand why they should
personally care about a scientific subject is often the first thing I consider when
planning a lecture. This study grant will provide me the opportunity to develop a
broader repertoire of examples and anecdotes I will use to engage students in the
subject matter. As we enter a revolution of personalized genomics we need a
prepared student population, particularly in the healthcare fields, to understand and
communicate this information to others. It is also relevant to engage students, who
are open to sharing all types of information through the web, about the uses and
challenges of genetic information. Primarily teaching microbiology, I often tell
students that this is the most important subject they will encounter in the
healthcare field, and while I am biased, this does not mean that I am wrong. With
the recent scientific interest in the human microbiome we have begun to appreciate
that microbes are not simply offending organisms, but an integral component of
human health. This is an area that has just begun to enter into educational
resources and is underrepresented in academic courses. A thorough review of these
related topics will enhance my current course content. I plan to use this
opportunity to develop a presentation that will be given to Collin students and
faculty in the Center for Advanced Studies in Math and Natural Sciences. I have also
contacted the educational director of the Medical Center of Plano and plan to
organize a presentation directed towards health care professionals regarding
advances in microbial interventions in the hospital setting.
The first aim will address the historical nature of sequencing technologies
from the discovery of the structure of Deoxyribonucleic Acid (DNA) to the first
sequenced DNA virus ϕ-X174 to the human genome and more recently the human
microbiome. An emphasis will be placed on the changing technologies that have
enabled this revolution and bring into focus the current bioinformatics bottlenecks
that are holding back this field.
My second aim will review some of the consequences of the sequencing of the
human genome in 2003: from the application of this knowledge to cancer
diagnostics to the Genetic Information Nondiscrimination Act (GINA) of 2008. The
human genome has given us a perspective to our biology that has provided
revelations, questions, ethical dilemmas, and at times a sense of genetic inadequacy.
The selected reading will provide a framework and variety of perspectives to these
issues.
The third aim will focus on the growing body of knowledge regarding the
relationships we have with the microorganisms in and on our body (collectively
called the human microbiome). From the human microbiome’s role in digestive
health and disease, to its influence on our immune system, the recognition that we
are intimately dependent on our microbiome is having a radical influence on science
and medicine.
I am proposing to carry out this study in the Fall of 2013, and it will consist
of the three aims mentioned above. A weekly study plan is outlined below.
Weekly study plan
Aim 1 – Weeks 1-3
The following will provide a greater perspective on the history and development of
sequencing technologies, with an emphasis on present technological bottlenecks. It
is very likely that at this time the Archon Genomics X Prize for the $1000 dollar
genome will have been awarded and new literature and commentary will be added
to this reading list as a consequence.
Davies, Kevin. The $1,000 Genome: The Revolution in DNA Sequencing and the New
Era of Personalized Medicine, Free Press, 2010
García-Sancho, Miguel. Biology, Computing, and the History of Molecular Sequencing:
From Proteins to DNA, 1945-2000, Palgrave Macmillan, 2012
Pevsner, Jonathan. Bioinformatics and Functional Genomics, Wiley-Blackwell, 2009
Aim 2 – Weeks 4-9
The following will provide a historical perspective on the use of genetic information
in medicine, with a focus on exploring the consequences of the publication of the
human genome. Within this aim I will also review the 2008 Genetic Information
Nondiscrimination Act (GINA) and its consequences, and explore the many
definitions of personalized medicine.
Collins, Francis. The Language of Life: DNA and the Revolution in Personalized
Medicine, Harper, 2010
Ewald, Paul. Plague Time: The New Germ Theory of Disease, Anchor, 2002
Gillham, Nicholas Wright. Genes, Chromosomes, and Disease: From Simple Traits, to
Complex Traits, to Personalized Medicine, FT Press, 2011
Gluckman, P., Beedle, A., & Hanson, M.. Principles of Evolutionary Medicine, Oxford
University Press, 2009.
Quackenbush, John. The Human Genome: Book of Essential Knowledge, Imagine!
Publishing (An Imprint of Charlesbridge), 2011
The Genetic Information Nondiscrimination Act of 2008, H.R. 493, 110th Congress,
2008
Aim 3 – Weeks 10-14
The following will provide an opportunity to examine the baseline studies on the
human microbiome, and explore the efforts to study and define the role of microbes
in human health and disease.
Cassader, M., Gambino, R., Musso, G.. Interactions Between Gut Microbiota and Host
Metabolism Predisposing to Obesity and Diabetes (Annual Review of Medicine), Annual
Reviews, 2012
Food Forum, Food and Nutritional Board, Institute of Medicine, Eds. Pray, L,
Pillsbury, L, Tomayko, E.. The Human Microbiome, Diet, and Health: Workshop
Summary, National Academy Press, 2013
Huffnagle, G., Noverr, M.. GI Microbiota and Regulation of the Immune System,
Springer, 2008
Littman, D.R., Honda, K.. The Microbiome in Infectious Disease and Inflammation
(Annual Review of Immunology), Annual Reviews, 2012
Relman, David. Microbiology: Learning about who we are. Nature 486, 194-195,
June 14 2012.
The Human Microbiome Project Consortium. Structure, function and diversity of the
healthy human microbiome. Nature, 486, 207-214. June 14, 2012.
Additional Materials
As this is a dynamic field, additional literature may be published that is relevant to these
topics. These will be added as appropriate and included in a final bibliography.
Bibliography
Cassader, M., Gambino, R., Musso, G.. Interactions Between Gut Microbiota and Host
Metabolism Predisposing to Obesity and Diabetes (Annual Review of Medicine), Annual
Reviews, 2012
Collins, Francis. The Language of Life: DNA and the Revolution in Personalized
Medicine, Harper, 2010
Davies, Kevin. The $1,000 Genome: The Revolution in DNA Sequencing and the New
Era of Personalized Medicine, Free Press, 2010
Ewald, Paul. Plague Time: The New Germ Theory of Disease, Anchor, 2002
Food Forum, Food and Nutritional Board, Institute of Medicine, Eds. Pray, L,
Pillsbury, L, Tomayko, E.. The Human Microbiome, Diet, and Health: Workshop
Summary, National Academy Press, 2013
García-Sancho, Miguel. Biology, Computing, and the History of Molecular Sequencing:
From Proteins to DNA, 1945-2000, Palgrave Macmillan, 2012
Gillham, Nicholas Wright. Genes, Chromosomes, and Disease: From Simple Traits, to
Complex Traits, to Personalized Medicine, FT Press, 2011
Gluckman, P., Beedle, A., & Hanson, M.. Principles of Evolutionary Medicine, Oxford
University Press, 2009.
Huffnagle, G., Noverr, M.. GI Microbiota and Regulation of the Immune System,
Springer, 2008
Littman, D.R., Honda, K.. The Microbiome in Infectious Disease and Inflammation
(Annual Review of Immunology), Annual Reviews, 2012
Pevsner, Jonathan. Bioinformatics and Functional Genomics, Wiley-Blackwell, 2009
Quackenbush, John. The Human Genome: Book of Essential Knowledge, Imagine!
Publishing (An Imprint of Charlesbridge), 2011
Relman, David. Microbiology: Learning about who we are. Nature 486, 194-195,
June 14 2012.
The Genetic Information Nondiscrimination Act of 2008, H.R. 493, 110th Congress,
2008
The Human Microbiome Project Consortium. Structure, function and diversity of the
healthy human microbiome. Nature, 486, 207-214. June 14, 2012.