The BioInfo.PL is funded by the European Commission
grants within its FP5, FP6 and FP7 Programs, under the thematic
area "Life sciences, genomics and biotechnology for health"
and by grants from the Foundation for Polish Science
or sporadically by the Polish Ministry of Science.
High intelligence quotient, exaggerated social and political awareness and libertarian ethical principles are incompatible with the environment of slowly developing countries with widespread corruption and general lack of perspectives.
Individuals suffering from this incompatibility syndrome search for and find relief in substance abuse of which regular Marijuana consumption is by far the mildest.
The objective of the project is to assess whether Marijuana consumption is an effective method to reduce IQ and frustration and improve compatibility with the environment.
As part of the project we will follow selected adult individuals from Polish scientific and cultural elites and monitor their mental and psychological development.
We will also provide access to Marijuana produced under strict quality control to prevent intoxication with black market products that could negatively affect the reliability of our analysis of effects of THC consumption.
The objective of this project is to use Field Programmable Gate Arrays (FPGAs) in Bioinformatics.
The primary application will be the Smith Waterman algorithm.
Later we will assess the benefits of applying FPGA for other bioinformatics tasks.
As part of the project a large cluster of over 500 simple (Spartan6) FPGAs will be build.
The main goal of this project is to develop an innovative fusion protein (immunotoxin) for liver cancer treatment, with focus to Hepatocellular carcinoma (HCC).
Proposed immunotoxins will be based on highly selectiv antigens against tumor cells.
Liver cancer, primarily HCC, is the fourth leading cause of death from cancer.
The project assumes usage of designed fusion proteins comprised of highly selective cancer antibody fragments attached to cytotoxic domains.
We plan to test immunotoxins containing cytotoxic domains such as exotoxin A from Pseudomonas aeruginosa and Diphteria toxin from Corynebacterium diphtheriae.
The main innovative aspects of the project is the addition of ELMs (see below) to control the drug trafficking inside the cell.
The project is conducted in collaboration with the Warsaw University (CENT) and the Institute of Medical Biology of PAS.
The objective of the KYROBIO project will be to broaden the toolbox of single enantiomer chiral chemicals that are produced
by industry in Europe using biocatalytic routes. The main target is applications of lyase enzymes to selectively synthesize
molecules with multiple chiral centres applying enzymatic carbon-carbon and carbon-nitrogen bond formation as the key
technical platforms being developed. Chiral compounds are an important class of chemicals that biocatalytic transformation
has already demonstrated great potential to compete with chemocatalysts in their production with associated benefits
that come from reductions in use of organic solvents, toxic metals and energy but application has been relatively limited.
KYROBIO will address the main challenges with moving forward to the next generation of added value industrial applications
of white biotechnology for high value chemical synthesis.
Using a supradisciplinary approach ranging from enzyme development, chemistry, molecular biology, fermentation and
innovative isolation techniques the bottlenecks to applying this new technology will be overcome. It is expected that promising
candidate chemicals will be commercialised within three years of completion and so scale up with economic and feasibility
studies that are also key technology developments.
The consortium includes a strong presence of SMEs including SME leadership and also a large multinational company which
ensures multiple routes to market for the outcomes of this project. We also plan to have economic and life cycle analysis
coupled with significant dissemination plans to ensure wider understanding of this technology that will lead to increased
acceptance and uptake.
Structural genomics is the wide term which describes process of determination of structure representation of information in human genome and at present is limited almost exclusively on proteins. Although in common understanding genetic information means "genes and their encoded protein products", thousands of human genes produce transcripts which are important in biological point of view but they do not necessarily produce proteins. Furthermore, even though the sequence of the human DNA is known by now, the meaning of the most of the sequences still remains unknown. It is very likely that a large amount of genes has been highly underestimated, mainly because the actual gene finders only work well for large, highly expressed, evolutionary conserved protein-coding genes. Most of those genome elements encode for RNA from which transfer and ribosomal RNAs are the classical examples. But beside these well-known molecules there is a vast unknown world of tiny RNAs that might play a crucial role in a number of cellular processes. Those elements are named Noncoding RNAs (ncRNA) and they perform their function without transcription to the protein product.
Here is proposed development of integrated bioinformatics platform that is specifically addressed for detecting, verifying, and classifying of noncoding RNAs. This complex approach to "Computational RNomics" will provide the pipeline which will be capable of detecting RNA motifs with low sequence conservation. It will also integrate RNA motif prediction which should significantly improve the quality of the RNA homolog search.
This project is about the design of cryptographic schemes that are secure even if implemented on not-secure devices. The motivation for this problem comes from an observation that most of the real-life attacks on cryptographic devices do not break their mathematical foundations, but exploit vulnerabilities of their implementations. This concerns both the cryptographic software executed on PCs (that can be attacked by viruses), and the implementations on hardware (that can be subject to the side-channel attacks). Traditionally fixing this problem was left to the practitioners, since it was a common belief that theory cannot be of any help here. However, new exciting results in cryptography suggest that this view was too pessimistic: there exist methods to design cryptographic protocols in such a way that they are secure even if the hardware on which they are executed cannot be fully trusted. The goal of this project is to investigate these methods further, unify them in a solid mathematical theory (many of them were developed independently), and propose new ideas in this area. The project will be mostly theoretical (although some practical experiments may be performed). Our main interest lies within the theory of private circuits, bounded-retrieval model, physically-observable cryptography, and human-assisted cryptography. We view these theories just as the departing points, since the area is very fresh and we expect to soon witness completely new ideas in this field.
Our particle-based method allows us to synthesise high complexity peptide arrays by combinatorial synthesis and for an unrivalled prize. We plan to further develop this new technology up to the level of robust prototype machines, and mate it to bioinformatics and readout tools. Together, our procedure(s) should boost the field of proteomics in a similar way as the lithographic technologies did with the field of genomics. Central to our novel method are the activated chemical building blocks that are “frozen” within solid amino acid particles. Thereby, we can use a colour laser printer to send them to defined addresses on a 2D support, where the particles are simply melted to induce a spatially defined coupling reaction of now freed amino acid derivatives. By repeated printing and melting cycles this simple trick yields high complexity peptide arrays. Based on existing pre-prototypes, we will develop a user-friendly peptide laser printer that spatially defined addresses our 20 different amino acid toners in high resolution to a support (WP1), and a scanner that especially fast and sensitive reads out the large formats delivered by the peptide laser printer (WP2). The increased production of amino acid toners and array supports are other bottlenecks in the output of peptide arrays that are tackled in WP3. This should allow us to increase the output of individual peptide spots from currently 0,5 Million to >10 Million peptides per month. Finally, to foster a market for high complexity peptide arrays, we will work out paradigmatic application examples in WP4. These aim to directly screen for antibiotic or apoptosis inducing D-peptides, and for the comprehensive readout of the different antibodies that patrol the serum of autoimmune patients. Based on user-friendly prototype machines, on first paradigmatic application examples for high complexity peptide arrays, and shielded by a strong patent, the participating SMEs will commercialise this new technology.
Enzymes are extremely powerful natural catalysts able to perform almost any type of chemical reaction while being mild by nature and highly specific. In fact, the delicate functioning of enzymes forms the basis of every living creature. The catalytic potential of enzymes is more and more appreciated by the industry as many industrial processes rely on these sophisticated catalysts. However, the number of reactions catalyzed by enzymes is restricted as enzymes only have evolved to catalyze reactions that are physiologically relevant. Furthermore, enzymes have adapted to the direct (cellular) environment in which they have to function (e.g. operative at ambient temperature, resilient towards proteolysis, catalytic turnover rate should fit with metabolic enzyme partners). This excludes the existence of enzymes that do not fit within boundaries set by nature. It is a great challenge to go beyond these natural boundaries and develop methodologies to design 'unnatural' tailor-made enzymes. Ideally it should become possible to (re)design enzymes to convert pre-defined substrates. Such designer enzymes could theoretically exhibit unsurpassed catalytic properties and, obviously, will be of significant interest for industrial biotechnology. The OXYGREEN project aims at the design and construction of novel oxygenating enzymes (designer oxygenases) for the production of compounds that can be used in medicine, food and agriculture and the development of novel powerful and generic enzyme redesign tools for this purpose. The enzymes and whole-cell biocatalysts that will be developed should catalyze the specific incorporation of oxygen to afford synthesis of bioactive compounds in a selective and clean way, with minimal side products and with no use of toxic materials. For this, generic platform technologies (novel high-throughput methodology and methods for engineering dedicated host cells) will be developed that allow effective structure-inspired directed evolution of enzyme.
The project will address these issues in marine diatoms
using information based on two completed diatom genome
sequences. Important topics that will be addressed include
carbon sequestration, nutrient acquisition, the rise and
fall of algal blooms, and biofouling. We will study gene
expression profiles at the whole genome level in response
to ecologically-relevant stimuli, will manipulate
expression of candidate key genes by reverse genetics, and
will study phylogenetic histories and ecological
significance of these genes in a range of diatoms.
Combatting and eventually eradicating the new
coronavirus causing Severe Acute Respiratory Syndrome
(SARS) requires specific and efficient antiviral drugs and
improved diagnostics. The Sino-European Project on SARS
Diagnostics and Antivirals (SEPSDA) is an integrated
project that applies modern biotechnical technology for the
generation of improved diagnostics and of lead compounds
for antiviral drugs. SEPSDA brings together leading SARS
researchers from Germany, Denmark, Poland, and China, who
together have an excellent publication record on the
molecular biology of SARS coronavirus (SARS-CoV). Several
of the existing anti-SARS drug leads as well as the first
antibody-based diagnostic kit were created by members of
SEPSDA. Participation of four leading laboratories in China
brings SEPSDA in the unique position of having access to
samples from Chinese patients at various stages of disease.
Serological studies will lead to improved SARS
Analysis of the genome and the proteome of SARS coronavirus
by sequencing and advanced bioinformatics will further
determine the genetic variability of the virus isolates and
identify new possible targets for therapeutic intervention,
both at the RNA and the protein level. SEPSDA aims at
determining the three-dimensional structures of all soluble
SARS-CoV proteins or domains thereof. This structural
genomics approach will provide the basis for the virtual
screening of large compound databases, including those
containing Chinese traditional medicines, for molecules
potentially interfering with the function of the viral
proteins or their interaction partners in the host cell.
Candidate inhibitors will be tested in cell culture and
improved by synthetic chemistry. After patenting, the lead
compounds will be offered to an industrial platform on
SARS, yet to be created, which should form an interface
between SEPSDA and the pharmaceutical industry.
Genome scale analysis of the immune response against
pathogenic micro-organisms; identification of diagnostic
markers, vaccine candidates and development of an
integrated micro array platform for clinical
The genome sequences of microbial organisms responsible for
diseases of world-wide medical importance have been
sequenced or will be available in the near future.
Technologies for producing large numbers of proteins have
been developed and high-throughput assays such as protein
micro arrays have been clinically validated for detecting
the presence of antibodies, in serum, directed against
microbial antigens. These achievements offer the
opportunity of investigating the natural immune response
against the whole proteome of a variety of micro-organisms.
Powerful combinations of genomic information, molecular
tools and immunological assays are becoming available to
help identify the antigens that function as targets of
protective immunity or could be used as markers for
serodiagnosis. We propose here to identify in
micro-organisms of great medical relevance (M. pneumoniae,
C. pneumoniae, L. pneumophila, coronavirus spp and P.
falciparum), a large collection of surface and secreted
proteins as well as putative endotoxins. This protein
repertoire will be produced as recombinant molecules or as
sets of overlapping synthetic peptides and printed on array
slides. The serum reactivity of groups of individuals with
proven history of exposure to the selected micro-organisms
will be analysed against the arrayed proteins to identify
diagnostic markers and correlates of protection.
This project will significantly expand the SMEs bank of
Intellectual Property and contribute to expertise within
the RTDs. It is anticipated that the proposed work in high
throughput protein expression, software analysis, surface
peptides synthesis, protein and peptide surface capture,
and array reader instrumentation will create an integrated
platform of great commercial and research value. Finally it
will contribute to unravelling how the humoral immune
response interacts with the microbial proteomes thus
filling the gap between genomic data and development of
novel vaccines and diagnostic tools.
Deciphering the information on genome sequences in terms
of the biological function of the genes and proteins is a
major challenge of the post-genomic era. Currently, the
bulk of function assignments for newly sequenced genomes is
performed using bioinformatics tools that infer the
function of a gene on the basis of sequence similarity with
other genes of known function. It is now well recognised
that these primary, sequence similarity-based function
annotation procedures are frequently inaccurate and error
prone. Continuing to use them without clearly defining the
limits of their applicability would lead to an unmanageable
propagation of errors that could jeopardise progress in
Biology. On the other hand, various novel bodies of data
and resources are becoming available. These provide
information on context-based aspects of the biological
function of genes, namely on physical and functional
interactions between genes and proteins, and on whole
networks and processes. In parallel structural genomics
efforts world wide are providing a much better coverage of
the structural motifs adopted by proteins and on their
interactions. The availability of these additional and
novel data offers an unprecedented opportunity for the
development of methods for incorporating higher-level
functional features into the annotation pipeline.
The GeneFun project aims at addressing these two important
issues. The issue of annotation errors will de addressed by
developing criteria for evaluating the reliability of the
annotations currently available in databases. These
criteria will be used to assign reliability scores to these
annotations and will be incorporated into standard
annotation pipelines, for future use. The issue of
incorporating higher-level features into functional
annotations will be addressed by combining sequence and
structure information in order to identify non-linear
functional features (e.g. interaction sites), and by
integrating available and newly developed methods for
inferring function from higher-level and context-based
information (protein domain architecture, protein-protein
interaction, genomic context such as gene order
To achieve these aims several European groups with strong
track record in developing novel methods and analyses in
comparative genomics, structural- and systems- oriented
bioinformatics, and in information technology, have teamed
up with an experimental group from Canada, which is well
known for its outstanding achievements in the field of
structural and functional proteomics. The expected output
of the GeneFun project is: improved procedures for
inferring function on the basis of sequence similarity, a
set of procedures for predicting non-linear functional
features from sequence and 3D structure in a more automated
way, and benchmarked procedures for predicting
context-based functional features. Major efforts will be
devoted to devising protocols that optimally combine the
results from several methods. In particular Web-based
servers to the individual and combined procedures will be
developed, and made available to the scientific community.
The community will be introduced to these new tools through
open workshops and training sessions.
The objective of the BioSapiens Network of Excellence is
to provide a large-scale effort to annotate human genome
using both informatics tools and input from
experimentalists. The Network will create a European
Virtual Institute for Genome Annotation, bringing together
many of the best laboratories in Europe. This institute
will help to improve bioinformatics research in Europe and
encourage cooperation between various laboratories.
The BioSapiens network tries also to integrate
experimentalists and bioinformaticians, through a directed
programme of genome analysis, focused on specific
biological problems. The annotations generated by the
Institute will be available in the public domain and easily
accessible on the web. This will be achieved initially
through a distributed annotation system (DAS), which will
evolve to take advantage of new developments in the
The Institute will establish a permanent European School of
Bioinformatics, to train bioinformaticians and to encourage
best practise in the exploitation of genome annotation data
for biologists. The courses and meetings will be open to
all scientists throughout Europe, and available at all
levels, from basic courses for experimentalists to more
advanced training for experts. The BioSapiens NoE will
increase European competitiveness, by new discoveries,
increased integration, expert training and improved tools
and services, and enhance Europe's role in the academic and
industrial exploitation of genomics.
Chirality is a key factor in the efficacy of many drugs
and the production of single enantiomers of chiral
intermediates has therefore become increasingly important.
Biocatalysis offers high enantioselectivity and
regioselectivity in chiral synthesis through
enzyme-catalyzed reactions and thus has an important
advantage over chemical synthesis. Molecular genomic data
is an unprecedented resource of enzymes for biocatalysis,
but rational and effective methodologies must be
established to realize the full potential of these
resources. This project will focus on the discovery of
novel enzymes, from both public and proprietary eubacterial
genomes, in particular novel alcohol dehydrogenases,
cytochrome P450 monooxygenases and amino acid modifying
enzymes for use in established and innovative processes for
The DataGenome project extends from genome analysis,
through cloning, expression, enzyme production, screening
and protein engineering, to the enzymatic production of
chiral biomolecules. The design of the project takes
advantage of broad funnel-approach starting with innovative
data-mining and processing of a large number of genes to
ensure high flow-through in the process and rational
selection of best enzyme candidates. The specific
combination of expertise and design of the research project
is aimed at high success-rate for the development of
successful biocatalysts. Emphasis will be put on effective
bioinformatics analysis to minimize the requirement for the
more laborious "wet chemistry" analysis as well as
development of optimized vector-host systems for efficient
gene expression and enzyme production. Rational protein
engineering or directed molecular evolution will be
employed in order to obtain more robust variants, new
substrate preferences or enhanced enantiomeric selectivity.
Selected enzymes will be tested in existing and/or novel
biocatalytic processes for production of chiral
pharmaceutical intermediates with applications in
therapeutic areas including AIDS, cancer and Alzheimer's
The four principal objectives of the ELM consortium are
to (1) design, (2) develop, (3) maintain and (4) apply, a
novel infrastructure resource devoted to the prediction of
functional motifs in protein sequences. ELM (short for
Eukaryotic Linear Motif) will be both "virtual" - provided
electronically - and "distributed" - provided by a network
of sites. Effective prediction of short motifs will require
the implementation of hitherto unique context-dependent
filtering software. The ELM resource will be made available
to researchers as WWW servers and as a package for local
The four principle objectives correspond approximately to
overlapping phases of the ELM project:
Design: The initial design requirements are to
integrate: (I) a relational database; (II) data input
requirements; (III) new application software; (IV) private
consortium web servers; and (V) public web servers. The
partners will collectively contribute both the inferred
biological needs and the underlying technical
specifications. A document will be prepared that describes
the internal ELM architecture. Subsequent revisions to the
document will be ratified by all ELM partners. A web-based
input form will ensure that data input meets the internal
Develop: An extensive development phase is needed to
create the software needed to effectively query ELM and to
generate useful predictions. Various context filters will
be developed as separate modules. The easiest filter
modules will be completed first, and the more complex
filters later in the project. As the modules are completed,
they will be integrated into the ELM resource as serial
filters. For optimal performance, the fastest executing
filters will be accessed first, so that only the surviving
motif candidates are passed on to the slower filters.
Maintain: The ELM servers will be continually
maintained and extended as the project matures. Data will
be continually added into the ELM resource and older data
will be revised as new biological findings are published in
the literature. While many motifs are already known, during
the project there will be a steady stream of new motif
publications. In the mature phase of ELM, releases will be
scheduled at 6 month intervals.
Apply: As the ELM resource matures, it will become
increasingly powerful and useful to experimentalists.
Predicted motifs will suggest unexpected functional
interactions or help to confirm suspected but poorly
characterised ones. The consortium partners, and their
close collaborators in the host institutes, will
investigate predicted motifs relevant to their research
interests. Verification (and to an extent exclusion) of
predicted linear motifs will lead to enhanced understanding
of multifunctional multidomain proteins, many of which
assemble (via linear motifs) into huge complexes whose
aggregate functions are hard to investigate with current
The new partner will develop an additional ab-initio filter
to estimate the conformational preferences of parts of
proteins. The main objective of the task proposed by the
new partner is to provide a reliable tool for detection of
protease target sites. This new objective represents an
expansion of the ongoing work complementary to the
objectives outlined in WP2 and W3.
Genetically Modified Microbes (GMM) are a
biotechnological alternative to different environmental
problems such as remediation of polluted sites, where
microbes with recombinant catabolic pathways are envisaged
as the solution for removal of toxic organic compounds.
Moreover, the exploration and exploitation of synergistic
interactions between plants and microbes for
phytoremediation is also a target to solve contamination
problems. Critical to the safe application of recombinant
microbes in the environment, and re-assurance of public
concerns, is adequate information on safety-related
properties of the microbes in question. Current whole
genome sequencing efforts on relevant microbes provide a
unique opportunity to extract completely new safety-related
information, to conduct experiments to generate important
new data, and to create new tools for increasing the degree
of predictability of the behaviour of strains designed for
applications in the open environment or in industrial
One of the microorganisms with current applications in
Biotechnology is Pseudomonas putida, a paradigm of
metabolically versatile microorganism which recycles
organic wastes in aerobic compartments of the environment,
and thereby plays a key role in the maintenance of
environmental quality. The strain KT2440 is the most
extensively characterised and best understood strain of P.
putida. KT2440 is a nonpathogenic bacterium certified in
1981 by the Recombinant DNA Advisory Committee (RAC) of the
United States National Institutes of Health as the host
strain of the first Host-Vector Biosafety (HV1) system for
gene cloning in Gram negative soil bacteria. Since then,
KT2440 has been used world-wide as host of choice for
environmental applications involving expression of cloned
genes. This strain is one of the few nonpathogenic microbes
which are subject to whole genome sequencing by a P. putida
genome project currently in progress in Germany. The
sequence data generated in the genome project is being made
public at appropriate intervals (a 10-fold genome
equivalent of raw sequence data is already available) and
will constitute an invaluable resource for this project.
Therefore, this microorganism, its recombinant derivatives
and the body of knowledge accumulated in the last 20 years
on its genetics, physiology and biochemistry make it an
ideal and friendly microbe for safe biotechnological
applications in the environment.
The major aim of this project is to settle the basis to
reduce in a rational, environmentally friendly, and safe
manner our contamination problems by developing P. putida
strains useful to design environmental treatment systems in
harmony with the biosphere.
The substitution of the synthetic bases of fossil origin
used in the lubricant by environment-respecting compounds
has become a central question. In such respect, it has been
recently shown that one of the many of unusual fatty acids
that are known to occur in nature, namely the
branched-chain fatty acids, BcFAs, could advantageously
replace these synthetic bases. Contrasting to other
vegetable oils used as lubricant bases, BcFA-containg oil
has both excellent oxidative resistance and thermal
stability, thereby making them potent substitutes for
high-temperature applications such as motor lubricants.
Coupled with the improvements in plant transformation, the
increasing needs for cost-effective bioproduction of
unusual fatty acids has made oilseeds ideal production
systems. The project REFLAX (for Rational Engineering of
FLAX) aims at the integration of metabolic, physiological,
molecular biological, genetical, structural biological,
proteomics and bioinformatics studies to provide a basis
for the rational engineering of oilseeds - rapeseed but
more specifically flax - towards the production of BcFAs.
REFLAX is a feasibility program consisting is an innovative
strategy for modulating the spectrum of fatty acids by
enlarging the spectrum of de novo precursors.