Program Director/Principal Investigator (Last, First, Middle):
Lander, Arthur D.
Background
Scientific revolutions are often heralded by two events. The first is a long period during which large
amounts of data are gathered that cannot be accommodated within traditional conceptual frameworks. The
second is a period of substantial influx of ideas and methodologies from other fields. Both are taking place in
biology today.
The last revolution in biology happened not so long ago: Roughly in the 1950s, and with much help from
physicists and chemists, Molecular Biology emerged, bringing fresh perspectives on the connections betweens
genes, proteins, and cellular behavior, and re-orienting a large part of biological research toward the genetic
and biochemical level. A legacy of molecular biology—the cataloguing of DNA sequences of human, animal
and plant genomes—has now given us a comprehensive view of the basic components of life and how they
interact with each other. The results have been at once exhilarating and terrifying. Able for the first time to
interrogate living systems in a comprehensive way, we biologists find increasing frustration in our inability to fit
life into neat, linear pathways that do well-defined jobs. We have been forced to confront the fact that the
building blocks of life are interconnected through vast layers of structural and functional interaction, wherein
every input triggers hundreds or thousands of outputs.
Complexity, of course, is not new in biology. In the molecular biology tradition, one strives to reduce
complexity by focusing on identifying underlying physical and chemical mechanisms. Yet the “new” complexity
in biology does not stem from a lack of mechanistic information. In fact, it is in areas in which we possess the
most mechanistic knowledge that our lack of real understanding has become most obvious. What so often
eludes us is not how molecules and assemblies work in isolation, but how they work together in useful
networks. The term “useful” is appropriate here because natural selection drives biological entities toward an
organization that fulfills purposes (survival, reproduction, etc.). Indeed, biological entities give the undeniable
impression of having been “designed” (without, incidentally, any need for a designer).
There is a growing awareness among biologists that the notion of design principles can provide an
organizational scheme by which biological complexity may be understood. Fundamentally, this is a view of
biology not just as physics or chemistry, but as engineering: networks of components and devices built to
carry out defined tasks reliably and efficiently in a less than fully predictable environment. To understand and
explain biology, according to this view, we must parse it into systems, high-level entities defined by the tasks
they perform. Such a holistic, top-down, engineering approach to biology is not exactly new (it is a mainstay of
physiology, for example), but it is such a departure from the reductionist/mechanist program of molecular
biology that it has recently acquired a name: Systems Biology. Arguably, it is the Systems Biology revolution
that is now upon us.
Defining Systems Biology
In recent years, many high profile articles about Systems Biology have appeared in the biological literature.
International meetings have sprung up and have become annual events. Graduate training programs have
been organized around the world. There are even new academic departments (most notably at Harvard) and
institutes (in Seattle and Japan, for example) of Systems Biology. Curiously, there is little consensus on what
the boundaries of Systems Biology actually are (the same could have been said about Molecular Biology
during its formative years). Yet, as Supreme Court Justice Potter Stewart once remarked about obscenity, we
may not be able to define it, but we “know it when [we] see it”. In the case of Systems Biology, what we see
are combinations of the following four features:
(1) Dynamics and modeling. Math, physics, chemistry, engineering, and computer science have developed
sophisticated tools for analyzing and modeling complex, dynamical systems. Until recently, only a small
fraction of biologists ever used such tools. The drive to understand complex, large-scale biological
organization is rapidly changing this. As a result, we are seeing an influx of practitioners from each of these
fields into biology, and a dramatic increase in the amount of modeling and computation in the biological
literature.
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(2) Quantitative experimentation. Experimental biologists are fond of telling their graduate students that any
effect less than two-fold in magnitude is not worth studying. This view (which would horrify a physicist)
illustrates the leanings of most present-day biologists toward qualitative, rather than quantitative, explanations
of phenomena. Yet only through the collection of reasonably precise, quantitative data can modeling, analysis
and computation be exploited to their full potential. Accordingly, a push for more quantitative experimentation
has become a hallmark of Systems Biology.
(3) Control engineering. Nobody understands design principles better than engineers. Within engineering,
the field of control offers a conceptual framework that is especially appropriate for understanding biology, as
well as an extremely powerful set of modeling, analysis, and optimization tools.
(4) Informatics and statistics. Complexity arises in biology from two sources: intricacy (small numbers of
elements with complicated interconnections) and massiveness (enormous numbers of elements). The
massiveness problem is acutely felt by molecular biologists, who are forced to interact with an ever growing
number of massive, genome-wide data sets (sequences, gene maps, expression data sets, alignments, etc.).
The need to manage (store, search, mine, update) massive data sets has drawn large number of computer
scientists to the informatics side of Systems Biology. The need to explore such data sets in the context of
multiple sources of variation and uncertainty has required the active participation of statisticians as well.
Systems Biology and Developmental Biology—New Partners or Old Friends?
Systems Biologists are currently taking aim at diverse topics in biological and biomedical research, such as
metabolism, signaling networks, gene regulation, genome evolution, cancer, and infectious disease. Of the 9
National
Centers
for
Systems
B i o l o g y that are supported by the NIH/NIGMS
(http://www.nigms.nih.gov/Initiatives/SysBio/Centers/), three have a strong focus on Developmental Biology:
one at Friday Harbor/University of Washington, one at Duke, and one here at the University of California, Irvine
(about which more will be said below). Questions within Developmental Biology that are being approached
from the Systems perspective include many of the most fundamental and longstanding in the field:
morphogenesis and pattern formation; growth control; cell differentiation; stem cell dynamics; cell migration
and guidance; gene regulatory networks; and the origins of complex traits.
Although Systems Biology is certainly opening up new avenues for addressing these questions, in many
cases it is more accurate to say that Systems Biology has re-invigorated modes of inquiry that have long been
a part of developmental biology. In morphogenesis, for example, the mathematical and computational
approaches of Systems Biologists (e.g. 1, 2-6) owe much to the early modeling work of Wolpert, Gierer and
Meinhardt (7-9). The gene regulatory network (GRN) approach to development also predates Systems Biology
(10, 11). Perhaps this is not surprising, when one considers that the long intellectual traditions of
Developmental Biology have always been far less constrained by reductionist/mechanist leanings than those of
Molecular Biology. Basic concepts of embryology like competence, regulation, determination, are all systemoriented. Waddington’s introduction of the notion of “canalization” of phenotype (12) long antedates the
modern Systems Biologist’s pre-occupation with bistability and “attractor states” (which amount to much the
same thing). To this day, experimental observations in Developmental Biology are frequently interpreted with
reference to the control of processes for the sake of achieving goals.
In fact, one of the first scientists to articulate a true Systems Biology view was a Developmental Biologist.
Paul Weiss (1898-1989), one of the early presidents of the Society for Developmental Biology, argued as early
as the 1920s against excessively reductionistic thinking in biology, ultimately stating, "It is an urgent task for
the future to raise man's sights, his thinking and his acting, from his preoccupation with segregated things,
phenomena, and processes to greater familiarity and concern with their natural connectedness, to the 'total
context'" (13). His prescient statement in 1950 that “the complex engineering performances of technology are
a much more pertinent model of the nature of morphogenesis than are the more elementary phenomena dealt
with in basic physics and chemistry,” strikingly prefigures the dominance of engineering concepts, such as
robustness and control, in modern Systems Biology (14)
Paving the Way for Change
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Despite historical links to Developmental Biology, many Systems Biologists understandably direct their
attention on the simplest organisms—bacteria and yeast—in which systems-level questions can be posed.
Technological advances are changing this, however. For Developmental Biology, the most important
breakthroughs are those that facilitate the study of systems that are spatially dynamic, i.e. in which processes
vary in space as well as time. For example, advances in imaging are facilitating real-time, quantitative
measurement of cellular and subcellular information in two and three dimensions. Advances in computation
and mathematics are facilitating the simulation and analysis of systems of partial differential equations, which
are generally needed to describe spatially dynamic events. As a result, Developmental Biologists are in a far
better position to incorporate Systems Biological approaches into their work than was true just a few years ago.
Yet new technology alone will not bring such a change about. This is because the skills needed to design,
execute and interpret Systems Biological investigations borrow heavily from fields like Mathematics, Computer
Science, Engineering, and Physics, in which most Developmental Biologists have little or no training. And to
most of the scientists in these fields, the skills (and even the vocabulary) of Developmental Biology are equally
foreign. Clearly, there is an acute need for cross-training. The proposed training program represents one of
several approaches that the University of California, Irvine is taking to accomplish this goal. The program
draws much of its strength from the fact that the Developmental Biology community and Systems Biology
community at UCI are both substantial, highly reputed, and already interacting productively with each other.
Developmental Biology at UCI
The UCI Developmental Biology
Center (DBC) was established as
the Center for Pathobiology in
1968, under the Directorship of Dr.
Edward A. Steinhaus. With the
transfer of the directorship to Dr.
Howard A. Schneiderman in 1969,
the focus of the unit shifted to
analysis of the mechanisms
controlling animal development,
which continues today. The DBC
has been home to major advances
in Developmental Biology over the
years, including many contributions
to the fields of pattern formation
and limb regeneration. The current
director of the DBC is Dr. J.
Lawrence Marsh, also a trainer on
this proposal.
The goal of the research
conducted in the DBC is to
understand the normal processes Fig. 1. Research Themes of the Developmental Biology Center
of development and homeostasis.
Abnormal development during embryogenesis is a common cause of birth defects, while abnormal
homeostasis is commonly associated with cancer or degenerative disease. The faculty in the DBC use a wide
range of experimental approaches to understand development (Fig. 1). The Center facilitates research by
providing access to state of the art instrumentation and by fostering events that spur the development of
interdisciplinary research. The center currently provides confocal microscopy, image analysis, flow cytometry
and cell sorting, surface plasmon resonance molecular interaction equipment and robotics. The center also
sponsors symposia, seminars and other gatherings to discuss both science itself and implications of the
science.
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Systems Biology at UCI
Although the emergence of Systems Biology has been a global phenomenon, a handful of academic
institutions have been at the forefront. At UCI, with its strong tradition of multi-disciplinary collaboration and
receptiveness to grass-roots research initiatives, a number of convergent efforts have helped secure a position
among these leaders.
The first attempt to organize Systems Biology at UCI was spearheaded by noted Developmental Biologist
(and now-Vice Chancellor for Research) Susan Bryant, who developed a proposal for a California Institute of
Systems Biology, in response to the governor’s call for Institutes for Science and Innovation in 2000. Although
the proposal was not funded, it helped prompt the incorporation of the Institute for Genomics and
Bioinformatics (IGB; http://www.igb.uci.edu/) as an organized research unit (ORU). The mission of IGB, which
focuses on the interface between computer science and biology, is to promote interdisciplinary programs,
foster innovative basic and applied research in biomedical informatics and computational biology, educate the
next generation of computational biologists, and support the public service and technology transfer mission of
the University. IGB is organized around seven areas of research and teaching: Biomedical Engineering;
Chemical Biology; Functional Genomics; Human Genomics; and Evolutionary Genomics; Structural Genomics
and Synthetic Biology; and Systems Biology. The IGB provides an administrative home and resources for
many interdisciplinary activities, such as summer training, seminars, symposia, workshops and meetings, and
seed funding for innovative research projects. IGB faculty have been successful at attracting grant funding for
interdisciplinary research administered by the Institute and through other campus departments. IGB also
administers a large NIH-sponsored Bioinformatics Training Grant (BIT).
As mentioned earlier, bioinformatics can be viewed as one of four major components of Systems Biology.
In 2001, a second center, the Center for Complex Biological Systems (CCBS; http://ccbs.bio.uci.edu/) was
organized to foster interactions among researchers focusing on the other three components. CCBS, which is
directed by Dr. Arthur Lander, initially came together to apply for a $450,000 NIH planning grant in Complex
Biological Systems research, which it received in 2002. These funds were used to support infrastructure
development and collaborations that led to several large research awards to teams of biologists and
mathematicians doing Systems Biology. CCBS also developed a proposal for a new “gateway” Ph.D. program,
entitled Mathematical and Computational Biology (MCB; http://mcsb.bio.uci.edu/), which welcomed its first
class of students in Fall 2007. This program combines training efforts from 9 departments in 5 schools, and
provides an avenue by which students from a variety of undergraduate backgrounds (math, physics, chemistry,
engineering, computer science, biology) can enter Systems Biology. Having just completed admissions for its
second year, MCB is attracting a strong, new applicant pool to UCI.
CCBS also developed a proposal in response to a joint call by the Howard Hughes Medical Institute (HHMI)
and the NIH for new training programs at the interface between biology and more quantitative scientific
disciplines. This $1M grant was funded at the start of 2006—UCI was one of only ten institutions chosen
nationally—and has been supporting the further development of MCB, with the eventual goal of evolving it into
a degree-granting interdisciplinary studies graduate program to be known as Mathematical, Computational and
Systems Biology, or MCSB (the distinction between “gateway” and degree-granting program is explained in
detail later in this proposal).
In early 2006, CCBS successfully lobbied to co-organize and co-sponsor, with Caltech, the Eighth
International Conference on Systems Biology (ICSB2007; http://www.icsb-2007.org), which was held at the
Long Beach Convention Center in October. ICSB is the oldest and most prestigious Systems Biology meeting,
and UCI sponsorship brought great visibility to the campus.
In August 2007, CCBS received a $14.5M P50 Center grant from the NIGMS, which designated UCI as one
of 9 National Centers for Systems Biology. This five-year grant provides support for research projects,
infrastructure development, seminars and workshops, as well as some support for graduate training in
Systems Biology. The overarching theme of the grant is Spatial Dynamics, and two of the three major
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research projects funded by the grant deal explicitly with animal development (most notably in the contexts of
pattern formation, growth, and tissue morphogenesis). At present, 54 faculty are affiliated with CCBS.
Since 2003, CCBS has sponsored annual off-site retreats devoted to Systems Biology research and
education. This spring, over 70 faculty, postdocs and students attended the two and a half day event. A
highlight of the event is a competition for new research collaborations, the winners of which are given $10,000
in seed money to initiate the work. Entries are solicited from the students, who only learn of the competition’s
theme area when they arrive at the retreat, and must come up with the ideas for collaborations before the
retreat ends. Entries this year included several in the field of Developmental Biology, including:
“Spatiotemporal Regulation of Epidermal Development”, a new collaboration between a biology lab and a
mathematics group.
“Generating a robust and sensitive transcriptional response to the Dpp morphogen gradient: Bioinformatic and
functional analysis of overrepresented sequences in the brk promotor,” a collaboration between a biology
lab and a computer science lab.
“Computational Modeling of Taste Papillae Patterning Using the Classic Turning-Meinhardt Model,” a new
collaboration between a biology lab and a mathematics group
“A domain growth model of how Dpp gradient controls the wing disc growth, considering mechanical stress,” a
new collaboration between a biology lab, a math group, and a biomedical engineering lab.
“Analysis of the TGF-beta/Notch Signaling Interaction using a Systems Biology Approach,” a collaboration
between a biology lab and a computer science lab.
Most recently, CCBS has been playing an active role in bringing new faculty in Systems Biology to UCI. In
2007, following a campus-wide competition, CCBS was allocated seven faculty positions to fill in Systems
Biology (over three years). To coordinate the
recruitment of these individuals—whose
appointments would ultimately be in
departments throughout the schools of
Biological Science, Physical Sciences,
Engineering, Information & Computer Science,
and Medicine—CCBS convened a Systems
Biology Council, with representation from
multiple departments and research units. The
first year of searches is currently concluding,
and 3 offers have been made. At least one of
these individuals focuses on the Systems
Biology of Development, and would likely be
added, after his arrival, as a trainer to this
Fig. 2. Participants at the 2008 CCBS retreat
program.
Research in Systems Biology of Development at UCI
Given UCI’s long history in Developmental Biology, it is not surprising that a substantial fraction of the
Systems Biology research at UCI is focused on Development. Several themes stand out in particular:
Pattern formation: Much research is being conducted on how morphogen gradients form, how they act, and
how they are able to perform robustly. At present the work focuses on fruitfly embryos and larvae; zebrafish
embryos; mouse brain, tongue and olfactory epithelium. Gradient systems studied include those formed by
BMPs, Wnts, Fgfs and retinoids. Much of the work involves the development of mathematical models of
morphogen transport and signaling that incorporate the complexity revealed by genetic experiments. Among
the program trainers involved in this work are Arora, Blumberg, Calof, Cho, Cramer, Fowlkes, Gross, Lander,
Marsh, Mjolsness, Monuki, Nie, Schilling, Wan, Warrior, and Yu.
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Growth control and tissue morphogenesis: Several projects focus on the role of feedback interactions in the
control of tissue growth, including the effects of spatial inhomogeneity on such feedback. Also studied is the
coupling between morphogen gradients and growth. Systems studied include mouse skin, brain and olfactory
epithelium, and Arabidopsis shoot and root growth. Among the program trainers involved in this work are Calof,
Dai, Lander, Mjolsness, Nie, Wan and Yu.
Gene regulatory networks in differentiation: Projects in several groups focus on the elucidation of largescale gene regulatory networks that control development. GRNs in early amphibian patterning are being
elucidated by Cho and Blumberg, whereas Xie is computationally defining mammalian genomic elements that
control regulatory interactions.
Stem Cells: UCI has a thriving Stem Cell Research Center (http://stemcell.bio.uci.edu), supported in part by
the California Institute for Regenerative Medicine, which just awarded $27M toward the construction of a new
61,000 sq. ft. building, and directed by trainer Peter Donovan. Systems Biological studies on stem cells are
focusing both on issues of proliferative dynamics (Calof, Dai and Lander), and genetic and epigenetic
regulation of gene networks (Yokomori, Cho, Bardwell, Donovan).
Biological Modeling: UCI has become a hotbed of developmental modeling, in part because of the
openness of mathematicians, computer scientists and physicists to collaboration. Areas of strength include
ordinary and partial differential equation models of reaction diffusion systems (Nie, Wan); adaptive threedimensional modeling of tissue growth and movement (Lowengrub); and discrete, stochastic modeling of
tissues (Mjolsness and Yu)
Birth Defects and Pediatric Medicine: Several systems biology projects focus directly on human
development and child health. Lander, Calof and Schilling work together on a component of an NICHD P01 on
Cornelia de Lange Syndrome, which is now known to be caused by decreases in the level of a key chromatin
structural complex that has been studied for several years by Yokomori, who recently joined the collaboration.
Because genome-wide effects are at the heart of this syndrome, Xie has also joined in to lend a bioinformatics
approach. Huang researches the gene regulatory networks underlying congenital heart defects, and Monuki
uses is currently using modeling to elucidate patterning defects underlying holoprosencephaly and other
craniofacial anomalies. Cooper has long studied the effects of lung immaturity (as occurs with premature birth)
on the later health of children, which has led him to focus on the gene regulatory networks that are activated in
neutrophils following exercise, and how these regulatory interactions differ in children vs. adults.
The above descriptions make clear that Systems Biology of Development is already a major research focus
at UCI. The proposed training program does not, therefore, rest on assumptions about new research
directions emerging. Nevertheless, the likelihood that this training program will foster further expansion of
research in the Systems Biology of Development at UCI is certainly high, given that it will strengthen the
qualifications of trainees who might do such research.
Existing Graduate Training Mechanisms at UCI
Venues for Ph.D. training in biological and biomedical research vary enormously among U.S. universities,
covering the spectrum from “old-style” department-centered graduate programs to huge pan-Campus umbrella
programs. One end of the extreme tends to provide greater educational coherence and personal attention; the
other tends to offer wider choice and opportunity for students to find out what they are interested in. As both
approaches have their merits, it is not surprising that UCI currently houses a patchwork of departmental and
interdepartmental programs, each with its own idiosyncrasies. This does not pose many problems for the
trainees (indeed, one could argue it gives them the benefit of many options), but it does complicate the process
of explaining how interdisciplinary training programs, such as the one proposed here, articulate with existing
Ph.D. training venues. The following “primer” on UCI training mechanisms is intended to help:
Entry points: Departments vs. Gateways. Ph.D. trainees are admitted to UCI either by Departments or
Gateway programs. A Gateway program is a 1-year program that is collectively managed by a group of
departments. At the end of the gateway year, trainees become identified with thesis advisors and
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automatically join the Departmental Ph.D. program to which their advisor belongs. Gateways allow students to
begin their Ph.D. training with a series of rotations in the laboratories of advisors in many different
departments. They provide common basic training for a group of students who will undertake somewhat
related research projects. There are currently three gateway programs (see Table 1).
The MBGB gateway (http://www.bio.uci.edu/academic/grad/mbgb.html): This is a large program managed
by seven departments in Biological Sciences and the School of Medicine. It takes in 55-60 students per
year, and has 138 faculty trainers. The acronym stands for Molecular Biology, Genetics and Biochemistry,
which are topics considered most basic to the curriculum. At present, the majority of students who study
Developmental Biology enter UCI through this Gateway, and end up in departments such as Developmental
and Cell Biology, Biological Chemistry, Microbiology and Molecular Genetics, or Anatomy and
Neurobiology.
The INP gateway (http://www.inp.uci.edu): This newer, smaller gateway program is focused on
Neuroscience (the acronym stands for Interdepartmental Neuroscience Program). It enrolls 5-10 students a
year, and they may join virtually any department on campus, including Neurobiology and Behavior, which
does not participate in the MBGB gateway. As developmental neurobiology is only one of many areas in
which UCI neuroscience is strong, a minority of INP students end up studying development.
The MCB gateway (http://mcsb.bio.uci.edu): The newest gateway at UCI, this one is focused on Systems
Biology (the acronym stands for Mathematical and Computational Biology). Unlike the other gateway
programs, it accepts students from many different backgrounds, and is designed so that students may join
both biology and non-biology departments (the latter being Physics, Biomedical Engineering, Math,
Computer Science) for their Ph.D. work. About 50 faculty participate in this program, which just admitted its
second class of students for fall 2009. The first class (7 students) is currently in the process of completing
the gateway year, so there are no statistical data on the areas into which these students will go. However,
given that many of the MCB trainers work on the Systems Biology of Development, we expect that a
substantial fraction of the students who receive support from the proposed training program will have come
through the MCB gateway. As stated earlier, there are plans to eventually develop the MCB gateway
program into a free-standing, degree-granting interdisciplinary program. In that event, it would effectively
function like a departmental program, i.e. students’ curricular requirements would be set by the program
throughout their entire period of training.
Departments that mainly accept students directly: The departments of Mathematics, Physics, Computer
Science and Biomedical Engineering participate in the MCB gateway, but most students join these
departments directly. The department of Neurobiology and Behavior participates in the INP gateway, but
most of their students join the department directly. The remaining departments relevant to this proposal
(Developmental and Cell Biology, Biological Chemistry, Anatomy and Neurobiology, and Pathology) ONLY
admit students through one of the gateway programs.
Multidepartmental training programs. Because students receive their degrees from departments, they must
fulfill curricular requirements that are department-specific. For those students who enter via gateways, the
specifics of how the mandated courses of the gateway year articulate with department requirements (e.g.
substituting for required or elective courses) are always pre-negotiated and made clear to the gateway
program students. In this way, every student knows at the outset what is required to graduate. For students
entering biology departments, gateway-year training usually constitutes the majority of didactic class work they
will take. In departments such as Mathematics, Physics, Computer Science and Biomedical Engineering,
substantial course loads are the norm through the second or even third year of graduate school.
In addition to needing to fulfill departmental requirements, many advanced students also come to join
training programs that cross departmental boundaries. Such programs are often supported by NIH T32, NSF
IGERT, or other training grant mechanisms (Table 3). They enable students to receive focused training within
a field relevant to their thesis work. As a condition of accepting training grant support, students agree to take
on additional curricular requirements. Such courses typically count toward “elective” credit in their
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departments. The proposed training program in Systems Biology of Development would operate in a similar
manner. It would not duplicate any existing training program at UCI, but would definitely benefit from the
existence of courses at UCI that were originally created to serve the needs of training programs in areas such
as Bioinformatics (the BIT training program), Developmental Biology, and Stem Cell Research.
Program Plan
The experience at UCI is that Systems Biology is less an interdisciplinary endeavor than a multidisciplinary
one. In other words, successful research emerges from teamwork between biologists who do experiments,
mathematicians who build and analyze models, computer scientists who carry out high level data analysis,
physicists who develop new theory, etc. This is quite a different approach to science than many of us in
biology are used to. How does one train for such a field?
Our approach to this question is guided by the conviction that training should not seek a homogeneous end
product. It is simply impractical to try to turn every trainee into someone who is simultaneously a top notch
experimental biologist, mathematician, physicist, engineer, and computer scientist. Rather, we must start with
students who are already heterogeneous in disciplinary orientation, and provide them with the cross-training
they need so that they can work effectively together in teams.
For trainees who have started down the path of experimental biology research, we need to give them an
appreciation for Systems approaches, and the skills to lead teams of modelers, engineers, data miners, etc.
For trainees who have started down the path to research in math, computer science, or engineering, we need
to teach them the vocabulary and philosophy of biology, and an appreciation of the technical possibilities and
limitations of experimental work.
From this two things follow: First, we must include among our trainees students who are enrolled in Ph.D.
programs in a variety of disciplines, not just those of experimental biology. Second, we must provide a
program curriculum that is, at least to some extent, tailored to individual needs. The need to fulfill these
objectives brings to the fore a third, equally important one: We must incorporate elements into our training
program that foster interaction and community among the trainees, so that they feel that they are part of a
coherent group. The program plan has been devised with an eye toward meeting these objectives.
a. Program Administration
The program director, Dr. Arthur Lander, will oversee the administration of the training program as a whole.
Dr. Lander has exceptional scientific and administrative expertise relevant to this program: Originally trained
as a neurobiologist and developmental biologist, his research has focused increasingly on the Systems Biology
of morphogenesis, growth, and birth defects. He has 10 years of experience as director of a T32 training grant
in Molecular and Cellular Neuroscience (from which he recently stepped down), as well as 8 years of service
as the Chair of Developmental and Cell Biology (which includes membership on the steering committee for the
MBGB gateway program). He served on the committee that founded the INP gateway program, and headed
the committee that founded the MCB gateway program. He is the director of UCI’s NIH National Center for
Systems Biology, and also serves as the program director of a three-year planning grant from the Howard
Hughes Medical Institute to foster the growth of the MCB program. He has a long-standing interest in graduate
education and the needs of graduate students, and served for 8 years on the Education Committee of the
American Society for Cell Biology. Dr. Lander has also served as chair of an NIH Developmental Biology study
section, and member of an NICHD branch review panel. Dr. Lander will devote 10% of his academic-year
effort to his duties as program director.
As program director, Dr. Lander will chair a steering committee that includes three other program faculty.
The job of the steering committee will be to solicit and select trainees; identify and assign trainee mentors and
co-mentors; and carry out program assessment. The committee will have the authority to add or remove
training faculty when justified, approve exceptions to training program policies when appropriate, and consider
revisions to the program curriculum.
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Members of the steering committee will be Dr. Frederic Wan, Dr. Thomas Schilling, and Dr. Dan Cooper,
who collectively add considerable experience in administration and graduate education.
Dr. Wan is a mathematician and mathematical biologist, who has previously served as Vice Chancellor for
Research and Dean of Graduate Studies, and currently serves as the director of the MCB Gateway program.
He thus brings wealth of administrative experience to the program, and provides a strong link between the
program and the MCB gateway.
Dr. Schilling is a developmental biologist, whose recent explorations of morphogenesis of the zebrafish
hindbrain have introduced a strong strain of mathematical modeling into his work. He has served for many
years as graduate advisor for the Department of Developmental and Cell Biology, and thus helps strengthen
the ties of the program to one of the major participating departments.
Dr. Cooper is Professor of Pediatrics and Biomedical Engineering, Chief of Pediatric Pulmonology, and
director of the UCI Institute for Clinical and Translational Science. He has recently begun to use to tools of
Systems Biology to investigate the gene regulatory networks underlying responses to exercise and stress. He
is currently in the process of establishing, with the assistance of CCBS and strong community support, a new
center for the Systems Biology of Pediatrics. He has a strong interest in promoting translational research, and
current serves as Vice Dean of Clinical Translational Science for the UCI College of Health Science (which
includes Medicine, Epidemiology, Nursing, and Pharmaceutical Sciences). His inclusion on the steering
committee builds important bridges to Pediatrics, and helps promote the view that Systems Biology does not
stop in the laboratory, but goes all the way from bench to bedside.
Administrative Support for the graduate program will be provided by the Center for Complex Biological
Systems. One of the two administrative personnel in the center is already devoted specifically to matters of
graduate education.
b. Program Faculty
Of the 26 program faculty named in
Table 2, 11 are Full professors, 8 are
Associate professors, and 7 are Assistant
Professors (one Assistant and one
Associate Professor are slated for
promotion this summer).
With the
exception of a few of the Assistant
Professors who are relatively new to UCI
and therefore do not have extensive
training or funding records, all of the
program faculty have a significant history of
training and adequate grant funding to
support the research of trainees (Tables 45).
The characteristic that unites this diverse
group of faculty—they represent 10
departments and 5 schools (Biological
Sciences, Medicine, Engineering, Physical
Sciences and Information & Computer
Science)—is that each can provide an Figure 3 Collaborations among training faculty. Collaborations
appropriate training environment for a that have already resulted in publications are indicated with red lines.
Ph.D. thesis that combines Systems
Biology and Developmental Biology. As discussed earlier, many of them—including appointees in both biology
and non-biology departments—are already doing just this. Others are engaged in interdisciplinary research
collaborations that are driving their research towards Systems Developmental Biology. Indeed, one of the
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Program Director/Principal Investigator (Last, First, Middle):
great strengths of UCI is the welcoming
attitude toward interdisciplinary
collaboration, an attitude that has
certainly helped foster the growth of
Systems Biology. Figure 3 graphically
depicts the recent and existing
collaborations among the training faculty
in Table 2. Red lines correspond to
collaborations that have led to joint
publications; blue lines are those that
have not yet done so. Note the central
positions occupied by the faculty in
mathematics, computer science and
physics (shown in green). Many of these
collaborations have been formalized
through joint research grants, including
joint R01s involving Nie, Wan, Warrior
and Lander; Bardwell, Nie and Yi; and
Calof, Schilling and Lander; as well as
research components of UCI’s National
Center for Systems Biology (P50) grant
that feature Bardwell, Calof, Cho, Gross,
Lander, Lowengrub, Marsh, Mjolsness,
Nie, Schilling, Wan, Yi and Yu. Other
evidence of the interdisciplinarity of the
training faculty can be seen in their
membership in relevant research
units—CCBS, the Institute for Genomic
and Bioinformatics, the Developmental
Biology Center, the Center for
Mathematical and Computational
Biology, and the Stem Cell Research
Center. (Figure 4)
Lander, Arthur D.
Figure 4. Membership of program faculty in Research Units.
CCBS, Center for Complex Biological Systems; IGB, Institute for
Genomics and Bioinformatics; DBC, Developmental Biology Center,
CMCB, Center for Mathematical and Computational Biology, ICAM,
Institute for Complex Adaptive Matter.
In addition to the faculty trainers listed in Table 2, there are a substantial number of established faculty at
UCI who are either Developmental Biologists that have not yet begun to make forays into Systems Biology, or
Systems Biologists who have not yet ventured into Development. Several of these individuals contribute to
teaching the courses that are part of this training program. As their research programs evolve, some of these
individuals could be added as trainers to this program:
Pierre Baldi Bioinformatics and Computational Biology
Emiliana Borrelli Dopaminergic system and glia in CNS development
Peter Bryant Cancer genetics and stem cells
Jorge Busciglio Cellular and molecular pathways in Down syndrome and Alzheimer's disease
Susana Cohen-Corey Synapse formation in the developing nervous system
Christopher Hughes Blood vessel development
Natalia Komarova Mathematical biology
Tony Long Quantitative and population genetics
Ulrike Luderer Reproductive toxicology, developmental toxicology
Grant MacGregor Molecular basis of mammalian spermatogenesis
Matthew McHenry Biomechanics, Locomotion, Sensory Biology
Ronald Meyer Neural regeneration
Diane O’Dowd Development of synaptic connectivity
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Natasa Przulj, Graph theory, mathematical modeling, and computational techniques
Jose Ranz Functional and comparative genomics
Robert Reed Evolution and development; butterfly wing patterns
Martin Smith Molecular and cell biology of synapse formation and plasticity
Georg Striedter Evolutionary Developmental Neurobiology
Leslie Thompson, Human Genetic Disorders
Kevin Thornton Genome evolution, gene duplication, population genetics
Douglas Wallace Mitochondria, Aging and Disease
Marian Waterman, Regulation of gene expression by LEF/TCF factors and beta-catenin
Dominik Wodarz, Mathematical & Computational Biology
c. Proposed Training.
The key components of the training program are didactic courses, discussion-based courses, dual
mentoring, and participation in community-building and career-preparatory activities. Trainees will be selected
from students who have completed at least one year of Ph.D. training, have passed any qualifying or
preliminary exams in their home department, and have committed to thesis research in the area of
Developmental Biology or Systems Biology, with a primary mentor who is a member of the training faculty
listed in Table 2. Generally, trainees will be selected who are at least two years from completing their degrees,
as the training activities of the program extend over two years. Likewise, it is expected that most appointments
for training grant support will be two years in duration (with the second year contingent on continued academic
good standing and suitable progress). Accordingly, the 10 positions requested here will typically support five
new trainees each year.
Trainees will be selected as described in section “e” (Trainee Candidates), below. Once selected, trainees
and their advisors would be asked to provide assurance of intent to complete the requirements of the training
program. Those requirements will vary somewhat, dependent upon the preparation of the student. The
description of program activities below is divided into two sections: activities common to all trainees, and
activities that vary depending on a trainee’s background.
1. Program activities common to all trainees
(i) Courses
“Systems Developmental Biology” (Winter). This one-quarter (10 week) graduate lecture course, to be
organized by program director Lander, is being developed primarily for this training program. It is an outgrowth
of an existing MCB core course “Systems Cell Biology (DC232; https://eee.uci.edu/08w/09332/)” in which Dr.
Lander currently teaches a three and a half week module on Development. Next Winter (Jan-Mar ’09), when
two of the other lecturers in Systems Cell Biology will be on sabbatical, Dr. Lander will expand the
Developmental Biology section to approximately 6 weeks, and when those faculty return for the 2009-2010
academic year, the course will split into two: a Systems Cell Biology course that is solely cell biology, and a
new “Systems Developmental Biology” course.
This new course will focus on Systems Biology approaches to major themes in Developmental Biology.
Background on experimental, computational or mathematical methods required to understand such
approaches will be taught as well. The goal of the course is to specifically acquaint trainees with the interface
between Systems Biology and Developmental Biology. A second goal is to build cohesion among the trainees,
by helping them define a common field of knowledge and interest.
Topics to be covered include those listed below Notice that the course is organized around processes and
strategies, rather than by organism, developmental stage, germ layer, or organ system.
Mathematica Basics
Sex Determination—introduction to positive feedback in cell differentiation
Cell Differentiation—gene regulatory network motif approaches
Cell Differentiation—global controls on gene expression
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Cell Differentation—Notch signaling
Growth control and tissue homeostasis
Stem cells and transit amplifying cell systems
Morphogens – History, formation of gradients, interpretation of gradients
Diffusion theory and gradient precision
Turing and Gierer-Meinhardt approaches to pattern formation
Left-right patterning as a Gierer-Meinhardt process
Noise in biological pattern formation
Facilitated transport of morphogens
Models of planar patterning (planar cell polarity)
Coupling oscillation with pattern formation: models of somitogenesis
Chemotaxis and chemotropism in development
Mechanical bases of tissue movements
Evolutionary origins of developmental strategies
Compensatory mechanisms for environmental variability
Lectures will be shared between Dr. Lander and three additional program faculty trainers (the lecturers and
topics will change somewhat from year to year to allow new topics to be introduced). As in the current Systems
Cell Biology course in the MCB program, students will be expected to carry out homework exercises that
involve modeling using the Mathematica software package, some of which will be individual projects, and some
of which will involve teams of students. Although the course will be primarily for students in this training
program, other graduate students will be permitted to attend.
“Critical Thinking in Developmental Biology” (Spring). This 10 week discussion class is also modeled
on a class currently taught in the MCB gateway program, which is itself based on a teaching model developed
over several decades at MIT and Princeton. The class meets once a week for 2.5 hours. The students are
assigned one pair of articles from the literature each week, and are expected to meet and discuss the papers
among themselves prior to returning to class the following week. In class, two faculty, working as team, lead a
discussion of the two papers, in which students are asked to critically “deconstruct” what was done, why it was
done, whether it was likely done in the order presented, how it was interpreted, etc. The pairs of papers
chosen each week are not drawn from the most current literature; rather they are selected for their didactic
value (e.g. they may be particularly elegant, or seriously flawed; or illustrative of an important method or
approach). Students participate solely by their input during discussion. The goals of the course include
training students in critical thinking and scientific method; helping the students identify the fundamental
methods and logic underlying the field of Developmental Biology; and helping to build cohesion among the
trainees in the program, by having them meet together, prior to the class, to analyze the assignments.
Typically, the pairs of faculty who lead these discussion rotate from week to week, and are selected so that
faculty who take very different approaches (e.g. experimental vs. modeling, biochemical vs. genetic, vertebrate
vs. invertebrate, etc.) work together. Although the papers to be taught will be chosen by the program faculty
who teach it, one can get a sense of the kinds of assignments that will be given by browsing the similarly
structured MCB course (“Critical Thinking in Systems Biology”) at h t t p : / / l a n d e r office.bio.uci.edu/CriticalThinking
(ii) Mentoring, assessment and evaluation
To be most effective, cross-training should be accompanied by dual mentoring. We will emulate another
successful cross-training program at UCI, the Bioinformatics Training (BIT) program, by assigning two mentors
to each trainee. Neither will be the trainee’s current thesis supervisor. In each case, one mentor will be an
experimental biologist, while the other will come from a mathematical, computational or engineering discipline.
The first job of each mentor team will be to meet with their trainee to assess his/her experience and needs.
This information will guide the selection of additional courses to be taken (see below). Mentors will also meet
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Program Director/Principal Investigator (Last, First, Middle):
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quarterly with their trainees to evaluate progress, and make recommendations regarding other activities (e.g.
journal clubs, grants to write, meetings to apply to, etc.). In many cases, one or both of a trainee’s mentors
may become part of the student’s thesis committee. Mentors who develop serious concerns about trainee
progress will inform the director and steering committee so that corrective actions may be taken (e.g.
counseling, tutoring, etc.)
(iii) Professional development and career guidance
The professional development of trainees will be fostered through a variety of activities. Journal
clubs—such as the Systems Biology journal club that was initiated by the MCB students (and is open to all), or
the Developmental Biology journal club that is run by the Department of Developmental and Cell Biology—will
provide an opportunity for trainees to hone their speaking skills. Another venue for student presentations is
“modeling lunch”, a monthly informal gathering focuses on issues in modeling biological systems, which is run
by faculty trainer Tau-Mu Yi. This has proved very popular with students, because presentations are often
arranged for the explicit purpose of soliciting new collaborations.
Trainees will also be encouraged to give presentations (oral or poster) at the annual retreats of the Center
for Complex Biological Systems and the Developmental Biology Center, as well as the monthly research-inprogress talks that the DBC organizes. In addition, the annual opportunity award competition at the CCBS
retreat (mentioned earlier; see also http://ccbs.bio.uci.edu/OppAwards.html) gives trainees an opportunity to
write short grant proposals for new collaborative pilot research projects, which begin as short abstracts
generated at the retreat itself, and are followed up by “full” (3 page) proposals that the trainees are asked to
submit 10-14 days later.
Most trainees will also receive instruction in teaching through a TA training workshop that is offered by the
school of biological sciences (Dev. Bio. 202B). Additional opportunities for training in teaching are provided
through an HHMI Distinguished
Professor Award to Developmental
Topic
Presenter
and Cell Biology Professor Diane
Resolving Conflict and Solving Professor Lisa Barron,
O’Dowd. One of the several
Problems Using Negotiation
UCI
innovative teaching programs she
Negotiating Resources: Learn to Ask Professor Lisa Barron,
oversees is a training program for
for What you Want
UCI
graduate students in becoming
Why Sex Matters
Dr. Judy B. Rosener, UCI
effective teachers.
Individual and Institutional Strategies Dr. Diane Wara
Training in the responsible
for Enhancing Advancement of
conduct of research is presented in a
Women in Academia
later section.
Opportunity to build career skills is
provided by a series of lectures
organized annually by the UCI
ADVANCE program (an NSF funded
program to promote institutional
transformation toward gender equity
by increasing the representation and
advancement of women faculty
across entire campus.). Lectures
given this academic year are shown
in Figure 5. These are usually
extremely well attended by students
and postdocs in many biological and
biomedical departments.
PHS 398/2590 (Rev. 11/07)
Professional Development and Academic Job Skills Seminars
The Application Process
Dr. Andrea Tenner, UCI
The Interview
Dr. Arthur Lander, UCI
Training and Career Structure in the Dr. Frank Solomon, MIT
Life Sciences
The Job Seminar
Dr. Thomas Carew, UCI
Sex in the Physical Sciences
Dr. Judy Rosener , UCI
Grant Writing Workshop
Dr. Sue Duckles, UCI
Negotiations Workshop
Dr. Butterfield & Jane
Tucker (Duke University)
Fig. 5. Annual career support lectures organized by the UCI ADVANCE
program
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Program Director/Principal Investigator (Last, First, Middle):
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2. Cross-training activities that depend on a trainee’s preparation
In addition to taking classes in “Systems Developmental Biology” and “Critical Thinking in Developmental
Biology”, each trainee will be expected to take two additional one-quarter classes, chosen from the following
two lists. These classes will be selected in consultation with the student’s mentors based on knowledge of the
individual trainee’s areas of deficiencies and the needs of the trainee’s proposed thesis research. Those
courses listed under Category I are designed to provide training in the mathematical, computational and
engineering foundations of Systems Biology. Those courses listed under Category II are intended to provide
training in the molecular biological foundations of Developmental Biology.
Typically, students whose initial training had been in biological disciplines would be expected to take two
courses from Category I (e.g. students who entered via the MBGB or INP gateway programs, or the
Department of Neurobiology and Behavior). Students whose initial training had been in the physical, computer
or engineering sciences, would be expected to take two courses from Category II (i.e. students who began
their Ph.D. training in the departments of Biomedical Engineering, Physics, Mathematics, or Computer
Science). Student who entered via the Mathematical and Computational Biology gateway program might take
a mixture of courses from Category I and II, depending upon their backgrounds, since they are likely to have
had more breadth, but less depth, in their classroom training than the other trainees.
In some cases, mentors may also recommend that trainees start out their first academic year in the program
by taking one or more of the short, informal “bootcamps” that are offered in early September (just prior to the
start of the academic year) to entering students in the MCB program. These bootcamps are full day training
sessions of between 3 and 14 days in duration, each intended as an initial, intensive introduction to a
discipline, for the benefit of students with little no background in that area. The three bootcamps that are
offered are (1) Mathematics; (2) Basic Biology and (3) Computation.
Courses in Category I
Mathematical & Computational Biology I Math 227A, Fall)
Introduction and Applications of Dynamical Systems (3 weeks), Introduction and Applications of Boundary
Value Problems in ODE (4 weeks); Calculus of Variations and Optimal Control for ODE (3 weeks)
Mathematical & Computational Biology II (Math 227B, Winter)
Method of Separation of Variables and Linear Stability Analysis for Partial Differential Equations (Wan, 3
weeks); Computational Methods in Ordinary and Partial Differential Equations (Nie, 3 weeks);
Mathematical Modeling, Analysis and Computation of Tumor Growth (Lowengrub, 3 weeks)
Computational PDEs, I, II and III (Math 226C, Spring)
Numerical methods for convection-dominated convection-diffusion equations; Introduction to spectral
methods; Computational fluid dynamics; Elliptic interface problem; Nonlinear optimization methods
Intro to Numerical Analysis and Scientific Computing, I, II and III (Math 225C, Spring)
Spectral methods and applications, Finite element method (FEM), finite volume method (FVM) and
applications; Computational Fluid Dynamics (CFD); Computational Quantum Physics; Computational
biology
Representation & Algorithms for Molecular Bio. (ICS 284A, Fall)
This course introduces state-of-the-art computational methods for studying modern biological systems.
Trainees study the principles of algorithm design for biological datasets, analyze commonly used
algorithms, and apply them to solve real-life problems. The course serves as an introductory course to the
rapidly growing field of computational biology and bioinformatics.
Probabilistic Modeling of Biological data (ICS 284B, Winter)
A unified Bayesian probabilistic framework for modeling and mining biological data. Applications range
from sequence (DNA, RNA, proteins) to gene expression data. Graphical models, Markov models,
stochastic grammars, neural networks, structure prediction, gene finding, evolution, DNA arrays single and
multiple gene analysis
Biological Networks (ICS 288A, Winter)
This course gives an overview of existing types of biological network data, points to sources of errors and
biases in the data, and introduces the current literature on graph theoretic modeling and discrete
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algorithmic analyses applied to these data. The course also presents an impartial overview of the works of
several major network biology labs around the world (e.g. Uri Alon, M. Vidal, J. Doyle, A-L Barabasi etc.).
Computational Math Methods for Systems Biology (ICS 284C, Spring)
A systematic approach to modeling biological systems for scientific purposes.
Scientific Computing (ICS282)
Computationally useful mathematical methods for science: Linear algebra and matrix decompositions,
optimization, differential equations, Markov chains and stochastic processes.
Dynamical Systems in Biology and Medicine (BME 233, Fall)
Introduces students to elements of system theory, and applies these principles to analyze biomedical,
chemical, social and engineering systems. Students use analytical and computational tools to model and
analyze various dynamic systems. Examples include: population dynamics, Lotka-Volterra equation,
Hodgkin-Huxley and Morris-Lecar equations, Belousov-Zhabotinsky chemical oscillators, etc.
Courses in Category II
Protein Structure and Function (Mol. Bio. 204, Fall)
The structure and properties of proteins, enzymes, and their kinetic properties.
Structure and Biosynthesis of Nucleic Acids (Mol. Bio. 203, Winter)
The structure and properties of nucleic acids. The fundamentals of nucleic acid hybridization and
recombinant DNA methodology. Replication and rearrangement of DNA.
Cell Biology (Dev. Bio. 231B, Winter)
An advanced, integrated view of cell biology. Topics include the cell cycle, the cytoskeleton, the
extracellular matrix, cell death, protein localization, signal transduction, and the cell biology of cancer.
Molecular, Cellular & Developmental Neurobiology (Dev. Bio. 231D, Winter)
Molecular aspects of the structure and function of neurons and glia including neurotransmission, synaptic
modulation, and channels. Neural development at the cellular and molecular level including neurogenesis,
pattern formation, trophic factors, axonal growth, and synaptic rearrangement.
Systems Cell Biology (Dev. Bio. 232, Winter)
This course introduces concepts needed to understand cell biology at the systems level, i.e. how the parts
(molecules) work together to create a complex output. Emphasis on using mathematical/computational
modeling to expand/modify insights provided by intuition.
Advanced Developmental Genetics (Dev. Bio. 210, Spring)
Advanced course on the use of genetic analysis to identify the genes that control cell behavior and
development. Formal discussion, by instructor, of genetics and the relationship between genotype and
phenotype, followed by student-led discussion based on assigned readings.
Regulation of Gene Expression (Mol. Bio. 206, Spring)
Aspects of gene expression including the organization of the eukaryotic nucleus in terms of protein-nucleic
acid interaction (i.e., chromatin and chromosome structure); comparisons between prokaryotic and
eukaryotic gene expression, the enzymology and regulation of RNA transcription in E. Coli and other
prokaryotes. Enzymology of transcription in eukaryotes.
Advanced Molecular Genetics (Mol. Bio. 207, Spring)
The course uses yeast as a model system to illustrate how powerful genetic and molecular approaches
have led to the current understanding of some conserved regulations of biological processes. It will also
introduce recent genomic approaches for gene discovery and functional analysis in the post-genomic era.
Chromatin Structure and Function (BC 225 Winter)
Topics include histone and DNA modifications and modifying enzymes, chromatin assembly and
remodeling, chromatin-mediated transcriptional regulation, genomic imprinting, X chromosome dosage
compensation, siRNA-mediated gene silencing, mitotic chromosome dynamics, chromosome territories
and nuclear matrix, and chromatin regulation in DNA repair.
Signal Transduction and Growth Control (BC212)
Covers various eukaryotic signaling pathways (tyrosine kinase, ras-raf-MAPK, TGF-beta, wnt, JAK-STAT,
and FAS) with an emphasis on the experimental underpinnings. The material is covered in lectures and
discussions of pertinent papers.
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Introduction to Proteomics (P&B 252/MBB 208 Fall)
Introduces students to concepts and methods of proteomics including protein identification, expression
proteomics, and protein-protein interactions.
d. Training Program Evaluation and Tracking
Evaluation
The proposed training program is unique, both in its focus on training at the interface between two fields,
and in several of the training strategies proposed. It will be important that the program undergo early and
frequent evaluation in order to determine which aspects are working well, and which need to be modified.
Ultimately, long-term evaluation—such as tracking the career trajectories of trainees—provides the most
reliable data on program success. However, evaluation on shorter time scales is more relevant to the year-toyear evolution of the program.
Before embarking on evaluation, it is helpful to build what professional assessors call a “logic model”, which
outlines the assets, strategies and goals of the program. This provides a roadmap of what needs to be
evaluated. Below is a brief logic model for the proposed training program.
“Inputs” represent the resources that contribute to the program. “Strategies” are the central elements of
program philosophy. As shown by the arrows, each of the program’s “Outputs”, or activities, can be traced to
some aspect of program strategy. “Outcomes” describe the goals that the outputs are intended to achieve.
“Impact” refers to the long-term effect of the program on the scientific enterprise. A major goal of evaluation is
to determine whether the desired outcomes are being achieved. However, for short-term evaluation, one often
also evaluates outputs by the criteria of whether they adequately follow program strategies, and whether they
are likely to produce desired outcomes. Keeping the connections between strategies, outputs and outcomes in
mind facilitates the process of choosing appropriate evaluation instruments.
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In general a combination of approaches of different types will be taken to evaluate the success of outputs
and outcomes. Currently, students who enroll in UCI classes are required to complete online evaluations at
the end of each quarter, giving feedback on course material, difficulty, instructor strengths and weaknesses,
and potential improvements. These evaluations will be supplemented with written material that the program
will solicit from the instructors who teach in courses taken by trainees as part of the program. Briefly, each
instructor will be asked, at the end of the quarter in which his/her course is taught, to evaluate the success of
the course that year, the effectiveness of recent changes to the curriculum or approach, and the quality of work
done by the trainees from this program.
The program will also turn to the two assigned mentors of each trainee for additional written evaluative
information at the end of each academic year. Mentors will be asked to provide information about time spent
with their trainee, an assessment of trainee progress, and an analysis of the impact of individual program
activities on the trainee’s academic development. The program will annually solicit evaluative information from
trainee thesis advisors, especially focusing on the perceived impact of the training program on the research
choices made by the trainee.
Although written evaluations can provide useful early feedback on potential issues needing attention, more
in-depth investigation usually requires extended conversations. Such conversations will be carried out in both
group and individual settings.
We have found that the annual CCBS retreat provides an excellent opportunity for group evaluative efforts,
and have used this mechanism repeatedly during the early development of the MCB gateway program. Briefly,
specific questions about program strategies and outputs are posed to all retreat attendees in open session,
following which attendees divide up into break-out groups of 15-20 individuals. During break-out sessions,
participants engage in a wide-ranging discussion, entering their comments in marker onto large flip charts.
Later in the general meeting, the flip charts from each group are brought to the front, and a representative of
the group goes over the major findings. A broad discussion ensues, during which extensive notes are taken
and later transcribed.
Although excellent, in-depth feedback can be obtained by this method, not all individuals volunteer opinions
freely in such public settings, and highly vocal individuals may dominate group dynamics. Accordingly,
obtaining evaluative information via one-on-one conversations is also important. This will be done informally
by mentors and the program director. However, if necessary (e.g. to resolve a specific question about the
success of a program output) we will ask independent interviewers to meet with and gather information from
both trainees and training faculty. A good source of such interviewers is available through UCI’s statistical
consulting center.
Tracking
In addition to the evaluation activities described above, the program will actively track the career trajectories
of all trainees for as long as possible following their departure from the program (and for a minimum of 10
years). Former trainees will receive yearly emails asking for updates about present position, publications,
grant proposals, and awards. Follow-up emails and telephone calls will be made to non-responders.
Database searches (e.g. PubMed, CRISP), and consultation of institutional web sites, will also be used to find
additional information. Periodically, trainees will be asked to send updated CVs.
The information obtained from tracking former trainees will be periodically analyzed by the director to
determine whether sufficiently positive outcomes are being obtained. In this context, “positive outcome” refers
not only to career success (did the trainee find suitable employment? has he/she been able to publish? Has
he/she obtained grants?) but also to meaningful incorporation of the training subject matter into the work the
trainee goes on to do. This information will be correlated with evaluative information that was obtained about
the program at the time the trainee was in training. Such correlation may help reveal whether particular
program strategies our outputs correlate strongly with positive (or negative) outcomes.
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Administrative assistance for tracking will be provided by staff of the Center for Complex Biological Systems
and the Developmental Biology Center.
e. Trainee Candidates.
Recruitment: Trainees will be recruited to this program from among advanced students (second year and
above) in the 9 departmental programs in which the training faculty participate (Table 1). Potential trainees will
be made aware of the program at a variety of stages during their early training through presentations during
initial orientation periods, in classes, and via email solicitations.
Trainers in this program will also actively participate in the recruitment of appropriate first-year students into
relevant gateway and departmental programs, in order to ensure a strong pool of potential trainees among the
students who join each of the departmental programs. For example, trainers will give presentations about this
training program to prospective students during interview days. In addition, one gateway program, the MCB
program, currently advertises itself via targeted emails to all students who have taken GRE exams in certain
subject areas during the previous year. The same email list will be used to send information about this
program and the various gateways through which a trainee might enter it.
Information about potential trainees, their numbers, their qualifications, and their distribution among different
programs may be found in tables 1 and 7-10. For 2008, component departments/gateways received
applications from 2375 individuals, made offers of admission to 412, and received enrollment commitments
from 184. Of those enrolling, 84 (46%) are training grant eligible (TGE). Slightly more than half of these are
headed for biology departments, with the rest headed into Math, Physics, Computer Science or Biomedical
Engineering.
Obviously, not all enrollees would be appropriate for this program. From Table 1 we can see that 12.5% of
all of the students enrolled in the 9 participating departments are doing their Ph.D.s with trainers in this
program. That enables us to predict an influx of 10-11 new, training grant eligible Ph.D. students into the
groups of the training faculty each year. However, some increase in recruitment seems likely, partly because
this program will likely attract new students to UCI, and partly because the relatively new Mathematical and
Computational Biology gateway program is growing rapidly (because of its subject area, MCB is especially
likely to be a source of students for this program). Even assuming no increase in recruitment, however, it
appears that there will be more than enough trainees available to justify the number of training slots requested
(which, as discussed earlier, would support 5 new trainees per year at steady state).
Trainee selection will be carried out by the steering committee, chaired by Dr. Lander. Trainees will be
solicited by open call to faculty trainers, as well as to students in appropriate departments, at least two months
prior to positions becoming available. The committee will review student admissions records, transcripts,
rotation reports, letters of recommendation from thesis supervisors, and relevance of the thesis research to
Developmental Biology and/or birth defects research. The committee will select the most highly qualified
students for whom the cross-training provided by the program would be likely to make a substantial difference
to the conduct of the trainee’s thesis research. Students whose selection would foster the goal of increasing
the representation of diverse groups will be specifically identified, so that diversity may be considered as a
factor in the selection process.
Data on the academic credentials of potential trainees may be found in Tables 8 and 9A. Figure 6 (below)
summarizes some of the data in Table 8 in a manner that facilitates comparisons across component programs
and department. Briefly, all programs are selective (admitting between 9% and 56% of TGE applicants) and
successful in enrollment (enrolling between 20% and 60% of admitted TGE applicants). Mean GPAs of TGE
enrollees vary between 3.34 and 3.71. GRE scores were unfortunately not always available in percentile form,
but the data show that they were typically above the 65th percentile for verbal and considerably higher for
quantitative. If one limits the analysis to the data in Table 9A (which includes only trainees currently working
with program trainers, or who are in first year programs and therefore could potentially do their theses with
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Program Director/Principal Investigator (Last, First, Middle):
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program trainers), then mean GPAs are 3.46+0.35 and GRE percentiles are V 64+24, Q 76+16. These data
do not include any MCB students, as the students of the first MCB class have not yet selected thesis mentors.
Table 7 documents the strong retention records of component departments and programs (note that, since
this table measures outcomes starting from initial admission, data for departments that admit solely via
gateway programs are included under the gateway programs). Table 5 documents that past trainees of the
program faculty have generally found good positions in academia or industry. Table 6 shows the publication
records of current and past pre-doctoral trainees, documenting the commitment of program faculty to
mentoring.
As shown in Table 7, the component gateway and departmental programs from which this training program
will draw have a good track record of recruiting and retaining qualified minority trainees. For example, the
MBGB consistently admits a class that is between 15 and 20% underrepresented minorities. The numbers for
several other programs are similarly high.
From Table 10, one can see that the individual trainers in this program have a similarly high record of
recruiting, retaining and advancing minority trainees. For example, out of the ~100 total TGE predoctoral
trainees of the program faculty over the last five years, 17 are underrepresented minorities.
Institutional Commitment.
As shown in the appended letter of support from UCI Dean of Graduate Studies Carolyn Boyd, UCI is
strongly committed to the success of training in Systems Biology and Developmental Biology. Institutional
stipend support is provided in the form of teaching assistantships and competitive fellowships during a portion
of a trainee’s education.
The campus also supports the efforts of this program indirectly through
1. Financial assistance to CCBS and DBC for administrative assistance
2. Allocation of new faculty positions to the area of this program (For example, CCBS was allocated, this
fall, seven new faculty positions in Systems Biology).
3. Guaranteed on-campus graduate student housing (for four years).
4. Centralized graduate admissions and record keeping.
5. Professional assistance in the preparation of large, multi-investigator grants.
6. Travel fellowships to allow students to attend scientific meetings at which they present.
7. Shared research resources and facilities (see Resources, pages 11-15).
Recruitment and Retention Plan to Enhance Diversity.
History and current efforts to recruit minority trainees (see Tables 8 and 10)
UCI pursues an active and diverse institutional approach to the recruitment of underrepresented individuals.
Campus-wide programs are coordinated through a “pipeline” that identifies promising high school and college
students and promotes an interest in basic research through seminars and laboratory research. This pipeline
is supported through grants from NIH such as the Orange County Bridges Program, the Minority Biomedical
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Researchers Program (MBRP), a Bridge to the Ph.D. Program, and the Minority International Research
Training Program (MIRT). Additionally, support has come from grants from the Howard Hughes Medical
Institute (Undergraduate Biological Sciences Minority Advanced Research and Training-UBSMART) and the
California Alliance for Minority Participation in the Sciences (CAMP), which is an NSF-supported, UCIcoordinated program of summer-in-residence research programs at multiple institutions.
Three different NIH-funded programs at UCI to increase minority recruitment in biomedicine fall under the
national award-winning institutional umbrella known as the Minority Science Program (MSP). The MSP
provides opportunities for laboratory research training positions for 40 undergraduate students and five
graduate students at UCI. UCI's excellent record in providing undergraduates with training in research was the
critical factor that led reviewers to select UCI to be a major participant in this new program. The MSP is
directed by Dr. Luis Mota-Bravo and has three full-time staff members to coordinate activities and help
students participating in its programs: The MSP Computer Facility has 20 networked computers, and a fulltime complement of student staff that provides computer instruction and guidance in word processing and
specialized scientific software. MSP staff has developed a network of UCI laboratories that provide research
training to student participants. Finally, to prepare students for these positions the MSP conducts research
methods workshops and a weekly seminar series featuring talks by UCI faculty researchers.
The O.C. Bridges to Baccalaureate program is a UCI collaboration with local community colleges (Orange
Coast College, Santa Ana College, and Santiago Canyon College) to give community college students
research experience in UCI labs. Laboratory experience is the best method to introduce students to scientific
research and thereby advance student careers in biomedical sciences. To make these opportunities attractive
and accessible, salary is provided for the time spent in the laboratory. Students in the Bridges to Baccalaureate
Program are placed in supportive laboratory working environments where they can establish peer/mentor
relationships. Participants are paired with junior and senior-year UCI undergraduate students, graduate
students, and other research mentors that have been supportive of underrepresented students in the past. One
goal is to encourage formation of new social and professional networks that can help community college
students establish acquaintances with biomedical professionals who can serve as role models/mentors. These
professionals can then write letters of recommendation and inform program participants of opportunities at UCI
(for graduate study) as well as at the university and private industry.
The Minority Biomedical Researchers Program (MBRP) from NIH (R25-GM55246) is a coordinated effort by
the faculty of the School of Biological Sciences and the staff of the Undergraduate Biological Sciences Minority
Advances Research Training Program (UBSMART) to increase the numbers of underrepresented minorities in
biomedical research positions. The MBRP began October 1996, was recently renewed, and will receive about
$2 million over the next 4 years to support 40 undergraduate researchers and five graduate students. Students
in good academic standing, interested in conducting research with UCI faculty, can apply in their sophomore,
junior, or senior year. After the initial training and orientation, MBRP undergraduates work in UCI research
laboratories while receiving salary for two summers of full-time employment and two academic years of parttime (10 hr./week) employment.
The MBR Program also offers incentives to attract underrepresented minority students to graduate
programs in the School of Biological Sciences and the College of Medicine at UCI. Incentives to continue in
the program at the graduate level include pay to assist in the workshops for incoming MBRP undergraduates,
an enhanced curriculum, additional training in scientific writing, travel funds, tuition remission, and release from
teaching duties.
The Bridges to the PhD Program is supported by grants from the National Institute of General Medical
Sciences (NIGMS). The aim is to increase the number of PhD researchers among the vast pool of untapped,
underrepresented talent in the Southern California area. The program complements existing transitional and
undergraduate training programs with similar objectives. Cal State LA, Cal State Fullerton and UC Irvine offer
the cooperative program leading to the MS degree and transitioning into a PhD degree at UC Irvine. Regularly
admitted students to the MS program at CSULA or CSUF are simultaneously conditionally admitted to the PhD
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Program Director/Principal Investigator (Last, First, Middle):
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program of their choice at UCI. On admission to the program, the Graduate Student Fellows are integrated into
active research groups under the direction of the training faculty. The student selects his/her own research
adviser at CSULA or CSUF, who consults with the student to match the nature and scope of the research
project to the student’s level and interests. All of the Cal State University faculty members involved in the
program are engaged in biomedical research, and normally the project selected by the student will lie in the
general area of the adviser’s current research interests.
Upon admission, the student also chooses a UCI co-mentor whose research interests roughly coincide with
those of the primary advisor. Through this co-mentor, the student is exposed to the research environment of
the doctoral institution by conducting research in the co-mentor’s laboratory in the summer, attending faculty
seminars, and taking science courses. Following completion of the MS program with a strong achievement
level, the student is guaranteed admission to the PhD institution for their doctoral studies, with financial
support. A yearly stipend and fringe benefits for each Graduate Student Fellow is provided. In addition, the
program provides: (1) payment of student registration fees; (2) $1,500 per year for research supplies, and (3) a
travel allowance for fellows to attend scientific meetings to present research papers. A participant’s tenure in
the MS program is a maximum of 2 years.
In addition, the UCI campus supports independently administered programs:
The Minority International Research Training (MIRT) Program provides undergraduate and graduate
biological, and biomedical science students, with international laboratory and field research experience. The
MIRT program also offers faculty the opportunity to establish and develop collaborative research projects with
faculty abroad. Participants receive course credit, room and board, transportation, and a stipend. The UCI
MIRT has provided international research training to more than 70 science students in three continents under
the supervision of world-known scientists.
The California Alliance for Minority Participation (CAMP) is a statewide initiative that aims to support and
retain undergraduates to achieve their degrees in the biological sciences, physical sciences, mathematics, and
engineering. Undergraduate participants in these UCI programs increasingly garner national awards for their
research work and scholarship.
To best facilitate communication with potential graduate applicants of underrepresented minorities in other
undergraduate colleges and universities, UCI staff travel nationwide to recruit underrepresented doctoral
applications from historically Black colleges, colleges with large populations of Hispanic and Native American
students, and the California State University Campuses in San Francisco, Hayward, and Sacramento, and
from Fullerton and Long Beach (institutions with a high percentage of minority students and easy access to
UCI). Staff, research faculty, and trainees have traditionally participated in national conferences such as the
Minority Biomedical Research Support (MBRS), Minority Access to Research Careers (MARC), the Society for
the Advancement of Chicanos and Native Americans in Science (SACNAS), the Annual Biomedical Research
Conference for Minority Students (ABCRMS), and California Forum for Diversity of Graduate Education
symposia. More recently the admission administrative officer for the Molecular Biology, Genetics and
Biochemistry (MBGB) Graduate Program has attended these meetings. Most of the graduate trainees for this
training grant are derived from the MBGB program.
Career support for women and minorities
At UCI, the commitment to increasing diversity does not stop at the admissions process. A new program at
UCI to foster success in women and minorities has been very helpful and well received. The UCI ADVANCE
Program for gender equity was funded by a $3.5 million grant from the National Science Foundation (20012006) with the goal of institutional transformation. The program is currently sustained by a 3 year, $500k
follow-on grant for dissemination of the practices developed during the initial period, along with generous
institutional support covering the staff, and programs such as the Equity Advisors.
The aims of the program are recruitment, retention and advancement of women tenure-track faculty. The
methodology is aimed at all levels, from high-level administrators to post-doctoral and graduate students,
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Program Director/Principal Investigator (Last, First, Middle):
Lander, Arthur D.
including career advising focus groups specifically geared towards graduate students and postdocs, and open
to all (not only women). By educating and raising awareness of equity and diversity issues, it is hoped that the
culture of the institution will move to one of inclusion and support for all colleagues. The message is as
important to students as it is to faculty, and to this end, graduate students and post docs are invited to various
workshops, conferences and mentoring programs, which should better prepare them to navigate through the
academic path.
Training in the Responsible Conduct of Research.
Training in the Responsible Conduct of Research is an essential component of graduate training in all
years. One formal aspect of that training is a required course, whose explicit purpose is 1) to meet NIH
training requirements for students supported on training grants, and 2) to introduce students to the complex
issues involving scientific integrity which will serve them in their developing careers as productive scientists
and academicians. This eight-week course is designed to engage students in discussion through the
presentation of background information related to scientific integrity, its critical role in the conduct of science
and a study of case histories
Each session in this course begins with brief remarks addressing the stated theme for the week.
Hypothetical and case studies are presented with time for discussion. Students are informed of campus
guidelines, such as the use of Human and Animal Subjects in Research, and provided with a Directory of
Contact Points on campus for specific issues. Additionally each laboratory on campus keeps a copy of Rules
and Regulations for the Conduct of Research, which is made available to all students. Trainees are required to
complete the course in Responsible Conduct of Research during their first year of graduate study. The course
coordinator position rotates among training grant program directors on a periodic basis. Tracking of student
enrollment and class participation will be performed by the program administrator. Additional instruction in
research conduct and bioethics is provided through a variety of less formal means, including discussions at lab
meetings, journal clubs, and departmental retreats. The Department of Developmental and Cell Biology
teaches a bioethics class for undergraduates, which some program graduate students will have the opportunity
to TA. A sample syllabus is presented below, showing faculty who are participating this year.
Responsible Conduct of Research, Lecture Schedule
MMG 250 - (http://jeeves.mmg.uci.edu/mmg250); 11-12 pm 4201 Nat. Sci II
Date
April 2
Topic
The Use of Animals in Research.
April 9
The Use of Human Subjects in Research.
April 16
April 23
Discussion
Research Integrity and Policies for
Handling Misconduct.
Data Collection, Record Keeping and
Ownership of Data.
Responsibilities of Authors and Reviewers.
What Constitutes Plagiarism?
Collaboration.
Discussion
Whistleblowing.
Ethical Issues in Stem Cell Research.
April 30
May 7
May 14
PHS 398/2590 (Rev. 11/07)
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Discussion Leader
James W. Hicks, Ph.D. Chair, UCI Institutional
Animal Care & Use Committee. Professor, Ecology
& Evolutionary Biology
Ruth A. Mulnard, R.N., D.N.Sc. Chair, UCI
Institutional Review Board C Director of Clinical
Trials, Institute for Brain Aging and Dementia;
Associate Director, Institute for Clinical Translational
Research
Group Assignments
Alan L. Goldin, M.D./Ph.D. Director, Medical
Scientist Training Program;
Professor of
Microbiology & Molecular Genetics
Rozanne M. Sandri-Goldin, Ph.D. Editor, Journal of
Virology; Chair of NIH Study Section; Professor of
Microbiology & Molecular Genetics
Group Assignments
Sidney H. Golub, Ph.D Former Executive Director,
FASEB Former Executive Vice Chancellor;
Professor of Microbiology & Molecular Genetics
Program Director/Principal Investigator (Last, First, Middle):
May 21
May 28
University/Industry Relationships and
Conflict of Interest.
Mentoring and Career Development.
June 4
Discussion.
Lander, Arthur D.
Kelvin W. Gee, Ph.D. Professor of Pharmacology
Sue P. Duckles, Ph.D. Associate Dean, UCI School
of Medicine, Professor of Pharmacology
Group Assignments
In addition to the Responsible Conduct of Research course, UCI sponsors the Howard Schneiderman
Memorial Lecture series in Bioethics. This series brings a distinguished guest lecturer to the campus each
year to talk about ethical issues in science. Recent examples include:
Stem Cells and Society: A Series of Dialogues (a series of public lectures), Francisco Ayala, PhD;
Peter Donovan, PhD; Hans Keirstead, PhD; Philip Nickel, PhD; Jennifer Terry, PhD
From Regenerative Medicine to Genetic Design: what are we really afraid of?, Gregory Stock,
Program on Medicine, Technology and Society, UCLA School of Public Health,
The Good Life at the End of Life, Joanne Lynn, The Washington Home Center for Palliative Care
Studies
Detentions, Ethical and Otherwise, in Scientific Progress, Harold T. Shapiro, President Emeritus
and Professor of Economics & Public Affairs, Princeton University
The Ethics of Stem Cell Research, Thomas H. Murray, Ph.D., President, The Hastings Center
Food Production and Nutrition Enhancement in the Golden Age of Life Sciences, Ganesh M.
Kishore, Ph.D., President Nutrition Sector and Chief Biotechnologist, Monsanto Company.
Is it Unethical to Clone a Human Being?, Dr. Arthur L. Caplan, Director of the Center for Bioethics,
University of Pennsylvania
Stemming the Tide: Politics, Policy and Regenerative Medicine, R. Alta Charo, J.D., Warren P.
Knowles Professor of Law and Bioethics University of Wisconsin Law School
Conflict of Interest in the Academic Medical Center - Is It a Problem?, Howard Brody, Ph.D.,
Director, Institute for the Medical Humanities, University of Texas Medical Branch
What's the Matter with Memory?, Elizabeth Loftus, Ph.D., Distinguished Professor of Social
Ecology, University of California, Irvine
Beyond Band-Aids: Curing America’s Sick Health Care System, Dr. Ezekiel Emanuel, Chair,
Department of Bioethics, The Clinical Center, National Institutes of Health.
Human Subjects
Some trainees may participate in research involving human subjects solely as part of other research
projects that have received or will receive IRB review and approval. No portion of the Training Grant Award
will be used to support this research. Below is a list of previously approved research projects and their IRB
approval dates or exemption designations.
PI/PD
Cooper
Cooper
Cooper
Huang
Title
Prevention Study Group Primary Prevention Trial
Assisted Exercise in Prematurity: Effects and Mechanisms
Trace Gases in Human Breath: Evaluation of Current
Collection and Storage Procedures
White Blood Cells, Exercise, and Children: Initial
Mechanisms
The Molecular Basis of Isolated Noncompaction of the
Ventricular Myocardium
Molecular Basis of Congenital Heart Defects
11/26/2007
2007-5805
Monuki
LHX2 Gene Mutations in Schizencephaly and Septo-Optic 02/21/2008
2003-2921
Cooper
Huang
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Approval Date
04/30/2006
01/01/1900
09/15/2005
Protocol #
2006-4873
2005-4797
2005-4338
07/12/2005
2004-3967
11/09/2007
2003-3130
Program Director/Principal Investigator (Last, First, Middle):
Monuki
Lander, Arthur D.
Dysplasia
Human Neural Stem Cells in Cerebral Cortical Development
06/22/2007
2005-4467
Vertebrate Animals
Some trainees may participate in research involving the use of live vertebrate animals solely as part of other
research projects that have received or will receive IACUC review and approval. No portion of the Training
Grant Award will be used to support this research. Below is a list of previously approved research projects
(grant number, PD/PI, and project title) and their IACUC approval dates or exemption designations.
Principal
Investigator
Protocol
Number
Last Approval
Date
Lander, Arthur D.
1998-1656
1998-1665
04/20/20008
03/02/2008
Regulation of Developmental Signaling
1998-1994
03/02/2008
Early-Life Experience-Evoked Neuroplasticity of
Hippocampal Structure and Function
2001-2303
12/13/2007
1999-1002
02/14/2008
MRI of Immature Rats
Nuclear Receptor Signaling
Development
2003-2487
01/11/2008
2005-2614
03/08/2008
2005-2618
02/08/2008
1998-1656
04/20/2008
1998-1658
03/20/2008
1998-1660
05/11/2008
Cho, Ken
1997-1254
10/30/2007
Trophic Factor Control of Neuron Production and
Survival
Signal Transduction during Gastrulation
Cramer, Karina
2002-2389
09/28/2007
Auditory System Development and Plasticity
Dai, Xing
1999-2133
01/25/2008
2006-2627
02/09/2008
2006-2679
01/10/2008
2002-2421
04/11/2008
Pluripotent Stem Cells in Development and
Disease
Breast Cancer Mouse Model of the tbx3
2005-2576
06/09/2007
Genetic Study of Retinal Degenerative diseases
Baram, Tallie Z.
Blumberg, Bruce
Calof, Anne
Donovan, Peter
Title
Early-Life Experience-Evoked Neuroplasticity of
Hippocampal Structure and Function
in
Vertebrate
Interactions between SXR/PXR and NF-kB
Signaling and their Impact on Inflammation, Steroid
Homeostasis, and Xenobiotic Metabolism
SXR, A Novel Target for Breast Cancer
Therapeutics
Organotin Activation of Retinoid X Receptor
Promotes Adipogenesis & Obesity
Regulation of Developmental Signaling
Regulation of Mammalian Neurogenesis
Role of Ovol (movo) and Wnt Signaling in Epithelial
Morphogenesis
Propogation of Mouse Strains
Huang, Taosheng
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Program Director/Principal Investigator (Last, First, Middle):
Monuki, Ed
2001-2304
11/08/2007
Schilling, Tom
2000-2149
02/01/2008
2006-2679
01/10/2008
2007-2771
01/29/2008
Lander, Arthur D.
Patterning of the Mouse Cerebral Cortex
Genetic Analysis of Pharyngeal Development in
Zebrafish
Pluripotent Stem Cells in Development and
Disease
Yokomori, Kyoko
Identification of Target Genes Critical for FSHD
Pathogenesis
Select Agents
None
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