Intellectual Development Statement
Thom LaBean
1) Research and Scholarship Development.
Completed. My professional work has been centered around structural biology issues concerning the evolution
and artificial engineering of biological macromolecules from several different angles. My Ph.D. dissertation work was
completed at the University of Pennsylvania under the tutelage of Stuart Kauffman (well-known author and theoretician)
and involved the examination of arbitrary sequence proteins for evidence of compact, folded structure. The project
addressed the relative roles of biological selection versus molecular self-organization in the evolution of stable
polypeptide structures. Examples of unevolved proteins were drawn from large random-sequence protein ensembles encoded
in chemically synthesized gene libraries; the design and construction of these libraries resulted in two US patents. My
final results (found surprising by many researchers) demonstrated that arbitrarily chosen polypeptides with random amino
acid sequences often display collapsed, partially folded conformations with significant levels of secondary structure.
My first post-doc projects also addressed the protein folding problem by testing our understanding of the rules
of folding through the de novo design of native-like structures and the redesign of tightly packed sidechain clusters
within the cores of natural proteins. I was fortunate enough to work with the world renown protein design team of Jane
and David Richardson at Duke University. During that time, I also helped develop a novel way of viewing the evolution of
biological RNA sequences as trajectories through nucleotide composition space with Erik Schultes who is currently at the
Whitehead Institute. Our collaboration resulted in three high-quality research articles. In my second post-doc, I moved
from protein structure design to DNA structure design and worked with John Reif (prolific theoretical computer scientist)
on design and construction of novel DNA structures intended to perform computations. This has evolved into my current
position in which I build and study novel DNA structures for applications in nanofabrication as well as computation.
In progress. My current research is aimed at understanding and manipulating the self-ordering processes and
metastable folded states of programmable molecular assemblies fabricated from synthetic DNA and other polymers for a
variety of nanoscience applications. I am interested in elucidating the rules of folding and association for de novo
designed DNA superstructures, and applying these insights to the development of smart materials capable of forming micron
scale objects displaying nanometer scale feature resolution. Technologies and materials being developed in current
projects may find application in nanoelectronics, molecular robotics, programmable medicines, smart materials, bio- and
chemo-sensors, molecular cryptography, and perhaps combinatorial chemistry encodings.
DNA-based nanotechnology seeks to utilize synthetic, linear oligonucleotides which base-pair to form branched
junction structures and component tiles which then associate with other tiles to form fabric-like molecular lattices
displaying desired patterns. The carefully designed structure may then be used, for example, as a template upon which
specific metal deposition can produce a nanometer-scale electronic circuit. The tagging of two components of a
nanostructure with complementary DNA causes (with high probability) those components to be situated near one another in
space, however, without the type of longer range associations inherent in our molecular tapestry systems, higher order and
longer length scale component organization does not seem likely. I have successfully designed , built, and analyzed DNA
molecular fabric able to form pieces 4 x 10 microns from a set of oligonucleotides of modest size (8 oligos, longest = 100
bases). My work is multidisciplinary and utilizes a wide variety of techniques such as chemical DNA synthesis, molecular
biology procedures, atomic force microscopy, transmission and scanning electron microscopy, chemical synthesis of metallic
nanoparticles, radioactive and fluorescent labeling of oligonucleotides, and electro-less metal deposition.
Present collaborations at Duke include work with: John Reif (Computer Science) on experimental and theoretical
studies on self-assembling DNA nanostructures for molecular computation and nanofabrication; Michael Pirrung (Chemistry)
on construction and manipulation of very large molecular databases encoded in DNA; Gleb Finkenstein (Physics) we currently
co-advise a Physics graduate student who is metallizing DNA nanostructures, etching contacts by electron beam lithography,
and measuring electrical properties of the constructs; Daniel Kenan (Pathology) on the use of DNA tile lattices to
organize kinetically active proteins for signal and power transduction in molecular machines and robots which may be
useful for sensorless sorting of nanoscale objects; Alvin Lebeck (Computer Science) theoretical and experimental study of
computer architectures enabled by current and future advances in nanoscience; Jie Liu (Chemistry) pilot study aimed at
combining carbon nanotubes with self-assembling DNA structures and proposed studies of catalyst patterning by DNA for
coordinated nanotube synthesis; Ashutosh Chilkoti (Biomedical Engineering) on computational analysis of protein
hydrophobic surfaces and proposed project involving DNA-based organization of environmentally responsive peptides; and
Jane and David Richardson (Biochemistry) on macromolecular engineering tools including computer modeling and display.
Future Directions and Strategy. I intend to continue thinking about DNA, RNA, and protein structures with
most of my time spent on engineering DNA nanostructures and mixed systems involving some proteins and perhaps RNA as well.
Future areas of focus will include diversified attachment chemistry options for immobilization of a wider variety of
materials upon DNA lattice sheets and patterning of catalyst moieties for coordinated growth of various reaction products
like single-walled carbon nanotubes and perhaps conducting polymers. Some interesting unexplored avenues could become
accessible given opportunities to apply to my current projects some aspects of my earlier work including combinatorial
polymer libraries and in vitro evolution techniques.
2) Teaching.
Philosophy and Goals. I have enjoyed my teaching experiences at Duke and look forward to putting together
a new course called “Biomolecular Nanotechnology” for the spring semester of 2004. Having taught only two courses so far,
my teaching style is still developing. I try to communicate lessons to students in the same ways I like information
presented to me. I like to learn primarily by reading and use lectures as reinforcement and review of facts and concepts,
therefore I tend to assign small reading assignments between every class meeting. Due to the cutting-edge nature of the
course topics, I have taught from current literature sources instead of textbooks; this serves also to help undergraduate
students become familiar with reading and extracting information from scientific monographs. I have found that take-home
and in-class projects as well as student presentations tend to engage the students and promote higher quality thinking
about topics than straight forward lecturing can achieve. Of course lecturing is also necessary, but my goal is not only
to impart new knowledge but also to connect the lesson of the day with other knowledge and interests already firmly held
by the student.
Strategy and Approaches. My approach to teaching has been influenced by the styles of effective teachers
from my past experiences. I try to bring eye-catching demonstrations or thought-provoking questions or puzzles as often
as possible for the beginning of class in order to gather everyone’s attention. I do not always succeed at finding such
teaching aids, but I am aware of the benefits of setting-up students for “teachable moments”, when they are attentive and
receptive. I have found that hands-on projects like building physical models of macromolecular structures are a sure way
of instilling a deeper understanding of the underlying lessons. I make extensive use of computer modeling and display
software too. I have been involved in the development of curricular materials illustrating three-dimensional structures
of macromolecular biomolecules using the program Mage (http://kinemage.bochem.duke.edu)
and so am able to tailor these materials to whatever molecules we are discussing. I have also learned the use of class
webpages to help organize and present course material.
Course Development Accomplished and Envisioned. I have taught “Computational Biology and Biomolecular
Computation” in 1998 and “Molecular Computing” in 2002 and I will be teaching “Biomolecular Nanotechnology” in 2004. I
was responsible for every aspect of these courses from inception to execution. They covered a wide range of information
from traditional computational biology (database searches, sequence and string matching, and protein secondary structure
prediction) to biomolecular computing (including DNA-based computing) and on to molecular electronics (including carbon
nanotubes, silicon nanowires, organic chemical moltronics, and metallic nanostructures). My new course envisioned for
2004 will also include an overview and specific details about self-assembling nanostructures for applications other than
nanoelectronics.
3) Service.
Secondary/joint/adjunct Appointments in Other Academic Units. Since my current work is of a highly
interdisciplinary nature, I foresee several adjunct appointments in the near future. I have begun the process of securing
an adjunct position in the Duke Chemistry Department which I’m certain will be mutually beneficial. My projects will be
positively impacted by the addition of students with interest and training in surface chemistry, metallic nanoparticle
attachment chemistry, and DNA modification techniques. Chemistry students who become involved in our group will be
exposed to new ideas in computer science, nanoscience, materials science, and physics. Jane and David Richardson have
spoken with me about the possibility of an adjunct appointment in the Biochemistry department, and we are currently
looking into the procedures and paperwork .Since I am co-advising a Physics graduate student with Gleb Finkelstein this
may be another logical department to look into.
Participation in Academic Enterprises and University Life. My interests and background training are quite
diverse, therefore I very much enjoy discussing other people’s research projects with them. I am serving on a space-
planning committee for the new engineering building and the Materials Governance Committee which oversees the set-up and
functioning of the Shared Materials Instrumentation Facility which is located in the basement of the LSRC building. I
also serve on the seminar committee for the Center for Bioinformatics and Computational Biology (CB^2). Membership on
these committees has exposed me to a broader cross-section of the university population and shown me more of the internal
workings of the university system.
Activities within the Discipline. I have served and am serving on program committees for international
DNA-based computing meetings as well as meetings on computational biology and genome informatics. I have acted as ad hoc
reviewer for a number of NSF grant applications, and reviewed manuscripts for several journals.