S16 Abstracts / Current Opinion in Biotechnology 22S (2011) S15–S152
PSL3
RNA-mediated transcriptional gene silencing in Friedre-
ich ataxia
Sanjay Bidichandani, Angela Castro, Yogesh Chutake
Department of Biochemistry & Molecular Biology, University of Okla-
homa Health Sciences Center, Oklahoma City, OK, USA
E-mail address: Sanjay-Bidichandani@ouhsc.edu (S. Bidichandani)
Friedreich ataxia (FRDA) patients are homozygous for an
expanded GAA triplet-repeat sequence in intron 1 of the FXN
gene. The expanded triplet-repeat results in transcriptional defi-
ciency of the FXN gene, which is reversed via administration of
histone deacetylase (HDAC) inhibitors indicating that silencing is
due, at least in part, to an epigenetic defect. FRDA patients show
repressive chromatin changes in the vicinity of the expanded GAA
triplet-repeat which results in deficient transcriptional elongation.
However, our data further indicate that FRDA patients also show a
defect in transcriptional initiation. Patients have repressive chro-
matin changes involving the +1 nucleosome, which is caused via
depletion of the chromatin insulator protein CTCF in the 5
UTR
of the FXN gene. Our results show that the repressive chromatin
leading to the initiation defect is mediated via RNA-mediated tran-
scriptional gene silencing. Interestingly, HDAC inhibitors currently
being used in clinical trials almost completely reverse the initiation
defect whereas they only partially reverse the elongation defect.
Our data have important implications for the pathogenesis and
treatment of FRDA.
doi:10.1016/j.copbio.2011.05.010
PSL4
Genetic and epigenetic approaches to understanding the
basis of human developmental anomalies
David R FitzPatrick
MRC Genetics Unit, Edinburgh EH4 2XU, United Kingdom
E-mail address: david.fitzpatrick@hgu.mrc.ac.uk
Anophthalmia (AN) represents to most severe developmental
eye defects where no globe is visible. The most common genetic
causes of AN are heterozygous, usually de novo, loss-of-function
mutations in SOX2 and OTX2 (accounting for 15% and 5% of cases,
respectively) and autosomal recessive mutations in STRA6 and
PAX6 accounting for ∼1% of cases each. High resolution array CGH
analysis will detect an abnormality in about 10% of cases. I will
discuss our early experience using massively parallel sequencing
in AN. Cis-regulatory mutations (C-RM) are an important cause of
human developmental disorders usually identified via molecular
characterization of chromosomal rearrangements, such as those
involving the region 3
to PAX6, result in a consistent phenocopy
of intragenic loss-of-function mutations in PAX6. At other loci C-
RM appear analogous to tissue-specific conditional knock-outs, for
example, mutations of cis-regulatory elements 5
of SOX9 causing
PRS as an isolated disorder. Interestingly duplication of the entire 5

regulatory region of SOX9 give a completely different distal limb-
specific phenotype. C-RM may also result in gain of function, for
example, misexpression of SHH have been described as a cause of
preaxial polydactyly. Human genetic analysis has a major role in
elucidating these fascinating genetic mechanisms.
doi:10.1016/j.copbio.2011.05.011
PSL5
Next-generation technologies to enhance cellular sig-
nalling network models aimed at drug design
James Bown
Centre for Research in Informatics and Systems Pathology, University
of Abertay Dundee, Dundee, UK
E-mail address: J.Bown@abertay.ac.uk
Biological processes such as growth, death, differentiation, and
migration are common to both normal and abnormal development
of multicellular organisms. Abnormal development arises when
the controlling mechanisms of these processes become dysregu-
lated. These processes are inherently multi-scale spanning gene,
intra-cell signalling network, cellular, tissue, and organism level.
However, complexity and scale-linkage remain key challenges to
articulating these processes. We consider the role of computer
games technologies together with rigorous cluster-based program-
ming techniques to address these challenges. While many models
exist to describe complex within-cell biochemical signalling pro-
cesses, and their response to drug interventions and mutations,
these models are difficult for the non-mathematician to work
with. We have developed a 3D games-based interactive visual-
isation to allow biologists to interact intuitively with such cell
signalling models. Translating a model into a form readily usable
by domain experts, rather than modellers, allows models to be
used for hypothesis generation to inform subsequent experimental
design, for example, drug design. Such models are useful descrip-
tions of a single cell. However these rich and detailed models do
not obviously scale up to the tissue-scale since the computational
requirements of constructing tissue-scale models comprising indi-
vidual cells with detailed signalling representations are ordinarily
prohibitive. We outline a framework that affords concurrent sys-
tems engineering to achieve this up-scaling.
doi:10.1016/j.copbio.2011.05.012
PSL6
Past, present and future of food biotechnology
Daniel Ramon
Biopolis SL, Valencia, Spain
E-mail address: daniel.ramon@biopolis.es
For thousands of years man has been applying genetics to
achieve the improvement of raw materials and final food prod-
ucts. Using selective breeding and/or mutagenesis, a large number
of plant varieties, animal races and microbial starters have been
produced. In fact, food biotechnology is the oldest biotechnology.
Recently, recombinant DNA techniques have been applied in food
technology creating the so-called ‘genetically modified foods’ (GM
foods), a class of novel foods. Transgenic potatoes useful as an oral
vaccine against cholera, recombinant wine yeasts able to produce
wine of increased fruity aroma and transgenic cows or ewes pro-
ducing milk with high levels of pharmaceutical proteins are some
of the results of the new food biotechnology. This new technology
differs in three respects to previous techniques: (i) directed change
versus the random nature of breeding, (ii) greater efficacy (less time
to obtain the desired change), and (iii) the possibility of crossing the
species barrier and thereby generating transgenic organisms. The
latter has important ethical and social repercussions. How success-
ful is this new technology? Last year, 15.4 million farmers planted
148 million hectares of biotech crops worldwide, especially in the
 Abstracts / Current Opinion in Biotechnology 22S (2011) S15–S152
U.S., Brazil, Argentina, India, Canada and China. However, oppo-
nents frequently argue GM food safety reasons and environmental
impact to reject GM foods and crops. What is there in all? This
is a technical debate that has become an ideological debate. All
GM foods in the market have been evaluated as recommended by
FAO or WHO and no problems of food safety have been detected.
A similar situation is present in the case of environmental risk.
Most important is the economic impact assessment. EU is against
this new agri-food technology. It is not the case for the rest of the
planet. As a consequence, EU is now an importer of GM food tech-
nology. It is important to remember that the first transgenic plant
was developed at the University of Gent with EU public founds. In
conclusion, the debate on GM food and crops is a multidisciplinary
discussion involving both scientists in experimental and social sci-
ences. It is time for European citizens to attend serious debate, free
of demagoguery.
doi:10.1016/j.copbio.2011.05.013
PSL7
Tumours markers, prognostic and diagnostic value
Mariapia Viola Magni
Perugia University, Perugia, Italy
E-mail address: ispatgen@unipg.it
We intend to consider the most diffuse tumour markers and
how the new molecular biological technique contribute in clarify-
ing their role. The most used markers will be reported and for each
one the limits of diagnostic and prognostic values will be analysed.
In particular they will be divided as newly secreted or substances
normally present in the blood which increase in case of tumour.
Their specificity with respect other pathologic diseases will be dis-
cussed. Another aspect that will be taken in consideration will be
the sensitivity: if their presence can indicate the presence of micro
metastasis and therefore may be useful for monitoring the tumour
development avoiding to use more expensive technologies. This
review will represent an updating analysis of the existing markers
suggesting also some new possible test which may improve the
results obtained until now. In fact not only the classical markers
will be indicated, but also some possible new ones which may be
present in the blood and may be studied using the new molecular
techniques. This analysis will permit to clarify the utility, sensitivity
and specificity of the markers and their future development.
doi:10.1016/j.copbio.2011.05.014
PSL8
Education in biotechnology and the life sciences: pro-
ducing fit for purpose graduates
Kevan M.A. Gartland
School of Life Sciences, Glasgow Caledonian University, Glasgow, Scot-
land, United Kingdom
E-mail address: Kevan.Gartland@gcu.ac.uk
Life sciences education develops graduates to meet a wide
variety of future economic, societal and technological needs. The
range of demonstrable attributes expected from graduates of life
sciences undergraduate and postgraduate programmes will be
discussed and related to the needs of industry and society in gen-
eral. Independent survey information provides guidance on which
attributes are key for biotechnology and the life sciences and
S17
contrasts with generic graduate attributes suggested for any disci-
pline. Particular emphasis will be placed on the contributions that
research-teaching linkages, employability and international expe-
rience make towards the educational development of graduates
able to innovate, lead and prosper in tomorrow’s harsh economic
conditions.
doi:10.1016/j.copbio.2011.05.015
PSL9
From recombinant proteins to
plant-made-pharmaceuticals
Eva Stoger 1 , Thomas Rademacher 2 , Elsa Arcalis 1 , Markus Sack 2 ,
Gabriela Stiegler 3 , Friedrich Altmann 1 , Rainer Fischer 2
1 University of Natural Resources and Life Sciences, Vienna, Austria
2 Institute for Molecular Biotechnology, RWTH Aachen, Aachen,
Germany
3 Polymun Scientific, Vienna, Austria
E-mail address: eva.stoger@boku.ac.at (E. Stoger)
The plant-based production of biopharmaceuticals has attracted
interest because plants, compared to traditional platforms for the
production of recombinant proteins, are inexpensive, highly scal-
able and safe. The number of products in development is increasing
as tools and strategies have been developed to accumulate recom-
binant proteins with specific glycan modifications in various plant
species and organs. Different platforms have been established
including transient expression systems, contained systems based
on cultured plant cells, and stable transgenic plants accumulating
recombinant proteins in leaves, seeds, fruits or tubers/roots. Plant
systems appear particularly suitable for the production of antibod-
ies that are required in large amounts. Antibody 2G12 for example
is one of a small number of human IgG monoclonal antibodies
exhibiting potent and broad HIV-1-neutralizing activity in vitro,
and the ability to prevent HIV-1 infection in animal models. We
have expressed this antibody in tobacco and maize, which could
facilitate inexpensive, large-scale production. The specific antigen-
binding function of the antibody purified from both plant species
was verified by surface plasmon resonance analysis, and in vitro cell
assays demonstrated that the HIV-neutralizing properties of the
plant-produced antibody were equivalent to or better than those
of its CHO-derived counterpart. Clinical studies with plant-derived
antibody are being initiated.
doi:10.1016/j.copbio.2011.05.016