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MV-BIO3_IMPACTreport2009 by hedongchenchen

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									IMPACT 2009 - MPBIS

“Strengthening of Bioinformatics and Systems Biology through
collaborations”

Report, edited by project leader Olle Nerman

2009-11-26



Background
The original version of this IMPACT project was funded in 2008, but delayed to
2009, because of lack of time for performing the projects. Thus parts of the
plans in the original project have been modified to better suit the current needs.
These modifications have been discussed with Patrik Jansson, in his role of
IMPACT project leader. The main points changed are that:

-The reform suggestions for MPBIS have been adapted to cope better with the
current policies of Chalmers with a quota for non-Chalmers students depending
on the number of Chalmers students and the constant threat of fees for non-EU
students.

-Moreover the larger group collaboration pilot project in connection to master
thesis writing has been substituted by support of a pilot project with
participation of a Gothenburg team in the competition iGEM.

This IMPACT report has three parts:

Part 1: On the future of MPBIS (Olle Nerman)

Part 2: Changes in course content of KMG060 and KKR063 (Jens Nielsen and
Goutham Vemuri)

Part 3: Participation in International Genetically Modified Machine competition
iGEM as a teaching development project (Sven Nelander and Anna Hallerbach)

We all thank IMPACT and Chalmers Foundation for the valuable financial
support!

Gothenburg 2009-11-25

Olle Nerman & Co
Part 1: On the future of MPBIS.
MPBIS today

The “Chalmers Master Programme in Bioinformatics and Systems Biology”
(MPBIS) is one of Chalmers´ smaller master programmes. It is also one of
Chalmers most international programmes with only a handful or fewer students
from Chalmers engineering programmes each year. It is uniquely multi-
disciplinar concerning both the student backgrounds and the spectrum of teacher
profiles. And the majority of the students are from non-EU countries. Despite its
size, the programme, and its forerunner in Bioinformatics, has played an
important role in establishing bioinformatics and computational biology in
Gothenburg and Sweden as a vital academic research and educational field.

Systems Biology in Gothenburg

Chalmers University of Technology and University of Gothenburg both have
high priority for developing experimental and theoretical systems biology on all
levels in the next years, and in this context the very small programme in
Systems Biology on University of Gothenburg (with only a handful of students
per round so far), and the systems biology profiles emerging inside Chalmers
Biotechnology Master Programme, are important components to consider. Thus
these programmes are also important in relation to any reform suggestions in
MPBIS.

Engineering Mathematics candidates

Moreover, the first round of students in Engineering Mathematics, a 5 year long
engineering programme, will in autumn 2009 start their third year. According to
the current plan there is an option for these students to have a substantial (15
hec) course in “Introduction to Molecular Biology, Bioinformatics and Systems
Biology”, as taught also in the MPBIS programme. This is scheduled in their
autumn semester of this third year. Subsequently these candidate students may
perform an applied bachelor project in a bio-topic in the consecutive spring
semester. Any reform of the MPBIS programme should be done with
recruitment of some of these very good students as an option.
Biostatistics?

Other options for specialization that is suitable, but not really planned for at the
moment, for these Chalmers students, are biostatistics and statistical
epidemiology (well-planned options for these study directions are currently in
place for GU-students). In this context also a couple of students per year with a
bachelor from Chalmers in Biotechnology are typically already interested in
specializing towards biostatistics.

General e-science

Many of the courses on the computational and statistical sides needed for
successful work in large scale statistics and data mining in biological and
medical contexts are highly relevant also for other e-science applications, and
one of the possible reforms is to broaden the purpose of the current programme
in order to cover more general e-science skills in a special recommended non-
biological direction. The MPBIS programme so far has been primarily research
preparing (on basic and advanced levels), and our feeling is that this is what is
required also for the e-science area. The students thought of here are of three
kinds, either they come from CS and need more statistics or they come from
statistics and need more CS/IT knowledge, or they have discipline specific e-
science research careers in other part of science or engineering in mind.

A possible expansion plan, and its implementation

After discussions with the main teachers in the programme in MV and D&IT
departments, and with Jens Nielsen at Biotechnology, and Patrik Jansson who is
a member in the committee for Chalmers e-science effort, I have suggested to
Bernt Wennberg (in his role of dean of education for all undergraduate
programmes in e.g. Physics, Chemistry and Bioscience and Mathematics) that
we should develop a detailed reformed curriculum for the programme along the
following lines:

   A) Broaden the curriculum to cover tracks with Biostatistics and general e-
      Science
   B) Change the order of the topics in the programme so that the first semester
      is devoted to CS/Statistics courses and delay the current bio-oriented
      courses to the second semester.

   C) Introduce options in the second semester towards three directions

       -Bioinformatics (with Cell Biology)
       -Biostatistics
       -Advanced statistics, data mining or other e-science CS courses

   D) And reserve the third semester to facilitate specializations towards

-Bioinformatics (and statistical genetics and genomics partly with GU)

-Systems Biology (mainly utislising biotechnology master programme courses)

-Advanced biostatistics (with GU)

-Advanced e-science (with MV and CS courses)



Recruitment to the reformed programme

The categories of Chalmers students that we target are

   -   CS and IT students
   -   Mathematical Engineers
   -   Biotechnology students
   -   Physics students

The MPBIS programme now recruits in an extremely multidisciplinary way
with some of the international students having relatively weak background in
mathematics and/or Computer Science. This new programme should have a
clearer ambition to recruit students with mathematics/CS courses on the level of
these four engineering programmes. Moreover, the first semester should have a
clearer bridging role concerning the basic quantitative techniques. Such a
curriculum will result in a better, and a slightly more equally prepared, group of
students. Thus the theoretical level in the specialization steps can be higher.
Name of new programme?

The naming of the reformed MPBIS programme, and the presentation of the
curriculum with tracks are both tricky questions that we also will address.

Committee and Time plan for the planning

The suggestion to Bernt Wennberg is that

Olle Nerman MV, Graham Kemp CS, Dag Wedelin CS, Petter Mostad MV, and
Rebecka Jörnsten MV form the committee. In January-March 2010, this
committee will in collaboration with the coordinators of the related master
programmes ( such as Biotechnology, Systems Biology at GU, CSALL)
develop the details and suggest a full plan of a reformed programme to GRUL,
that if received positively should be implemented from autumn 2011.



Olle Nerman
Professor and coordinator of MPBIS


Part 2: Changes in course content of KMG060 and KKR063 at
Chalmers
In connection with the recruitment of Prof. Jens Nielsen to Chalmers University
of Technology and establishment of a larger research group on Systems Biology
at the university, there has been introduced a number of changes to the two
courses KMG060 Data Acquisition and Handling in Systems Biology and
KKR063 Metabolic Engineering in order to bridge further with the research
activities of the new group. Furthermore, changes have been introduced such
that there is an improved coordination between the two MSc programs on
Biotechnology and Bioinformatics and Systems Biology at Chalmers. The
changes in the two courses are described in more details below.

KMG060 Data Acquisition and Handling in Systems Biology
Previously the course was offered by teachers affiliated with Gothenburg
University, and focus had been on high-throughput data acquisition and less on
data analysis and integration of data using systems biological tools. The course
was run as a joint course with the MSc program on Systems Biology at GU, but
many of the Chalmers students found that the course lacked elements of
quantitative analysis. The course has therefore been completely redesigned such
that it covers three major themes:

   1. High-throughput data generation (omics analysis) and data analysis.
   2. Mathematical modeling of metabolism.
   3. Integrative analysis

The first theme covers the topics: genomics, transcriptomics, proteomics and
metabolomics. Two completely new exercises will be designed, one on
comparative genome analysis including ORF identification and analysis, and
one on analysis of transcriptome data using different normalization methods,
clustering techniques and statistical methods. The lectures will give an overview
of the methods and a number of practical examples will be presented, mainly
based on the experimental model system yeast Saccharomyces cerevisiae, but
examples from other fungi and higher eukaryotes, e.g. mouse studies, will also
be given.

The second theme covers the topics: reconstruction of metabolic network
models, linear programming, dynamic models, topology of metabolic networks,
identification of extreme pathways and identification of elementary flux modes.
Three completely new exercises will be developed, one on linear programming
and model simulations, one on dynamic models and one on elementary flux
modes and extreme pathways. The lectures will present the fundamental theory
and give several different examples of metabolic models, mainly based on
studies with the yeast S. cerevisiae, but examples from other cellular systems
will also be presented.

The third theme covers the topics: integration of thermodynamics for
constraining metabolic networks, integrated data analysis using metabolic
network models and examples of integrated analysis from industrial
biotechnology and systems medicine. One new exercise will be developed. This
exercise will demonstrate how transcriptome data can be analyzed in the context
of metabolic networks with the objective to find co-regulated modules in
metabolism. The lectures will give different types of examples and describe the
basic theory of the different types of analysis.

In connection with the redesign of the course a set of learning
outcomes/teaching objectives have been defined for the course overall and they
will be designed for each of the lectures. The overall teaching objectives are
enclosed.

KKR063: Metabolic Engineering

The Metabolic Engineering course that has been offered at Chalmers was
provided the students with a detailed perspective only on using linear models to
study microbial metabolism. The students made a particular request to include
other methods to study microbial metabolism. Considering the request and the
limitation of the course, the principal change that was made to the course was in
its underlying philosophy. The course will focus on the different strategies that
are available to design microbial metabolism to suit the desired metabolic
objective.

The revised version of the course, due to start in March-2010, will emphasize on
using engineering principles to design microbial metabolism. Different kinds of
mathematical modeling strategies that are used to quantify metabolism will be
included in the course. The nature of information that these models provide will
be extensively discussed using assignments and classroom discussions. New
exercises have been designed to help the students understand these models. A
particular focus of the course is to help the students make a judicious choice of
the modeling strategy to meet the design objective. The modeling strategies to
be included in the course are divided into steady-state models and dynamic
models. The pros and cons of the two kinds of models will also be discussed. A
thorough introduction to the following quantitative methods along with
exercises in each method will be included in the revised course.

Steady-state metabolic modeling

1. Stoichiometric model of metabolism: A simplified stochiometric model of
   metabolism will be introduced to describe substrate consumption and
   product formation in microbial cells. This will serve as an introduction to the
   subsequent topics.
2. Flux balance analysis: An introduction to linear programming is included. A
   higher resolution network of metabolic reactions will be considered here.
3. Genome-scale metabolic modeling: The above concepts will be expanded to
   consider every single reaction that is present in the organism to analyze how
   the deletion of a certain gene impacts other parts of the metabolism on a
   global scale.
4. Elementary flux modes: The different combinations of the reactions of how
   a substrate could be converted into a product will be evaluated in this topic.
   These combinations will be evaluated for their efficiency, and the trade-off it
   has on the cell.

Dynamic modeling of metabolism

5. Kinetic modeling: This new topic will emphasize on the kind of information
   that can be obtained using dynamic models and not from steady-state
   models. Using mass-action kinetics of enzymatic reactions, a detailed kinetic
   model of metabolism will be introduced.
6. Metabolic control analysis: An extension of the dynamic models will include
   a detailed analysis of the kinetic models by determining the variables that
   control metabolism.

In addition to the lectures and exercises, the new version of the course will also
have a group project that will require them to work on a real-life problem and
present their results.

The light of the major refurbishing of the course, new exercises have been
developed to correspond with the lectures. As a result, a description of the
course with a detailed plan of the lectures, exercises, assignment and the
learning objectives is being prepared and will be made available in due time to
attract students.



           Jens Nielsen                                   Goutham Vemuri
           Professor                                      Forskarassistent


Part 3: Participation in International Genetically Modified
Machine iGEM as a teaching development project

Supervisor perspective
International Genetically Engineered Machine (iGEM) is a biotechnological
competition hosted every year by the Massachussetts Institute of Technology
(http://2009.igem.org/Main_Page).

The aim of iGEM is to promote research education in a particular branch of
biotechnology called ‘synthetic biology’, which aims to design, implement, and
analyze artificial (synthetic) molecular biological system. Besides its
interesting scientific connection to an emerging field, iGEM is an
interesting teaching experiment, with the central idea to form
interdisciplinary teams of around 10 students with different types of educational
background. The 10 students work together for 3-6 months, and the expected
output is a design of a synthetic biological system. Teams who want to attempt
actual construction of their system are encouraged to base their constructions on
a particular technology distributed by iGEM headquarters; this technology is
essentially a set of 3000 DNA plasmids, each plasmid containing a biological
component that can be combined with other components. Typical iGEM projects
involve e.g. bacteria that change color with the chemical environment, or design
of circuits with particular properties, e.g. chemical oscillators.

The Gothenburg iGEM 2009 team was formed by students Anna Hallerbach
(computer scientist) and Naser Monsefi (molecular biologist). Both are
Master’s students in the GU/Chalmers Bioinformatics and systems biology
Master’s program and the team comprised six other students with different
background and nationality. The time-line of the project was as follows:

April 2009: AH and NM started forming a team and identified mentors, in this
case Sven Nelander (FoAss, GU) and Per Sunnerhagen (Professor, GU).

May-June 2009: The team worked with mentors to design a project. Based on
an idea from the students, who were rather theoretically oriented, was to study
whether it is possible to make bacterial cells perform a particular algorithm
from theoretical linguistics referred to as sentence parsing. This struck the
mentors as a very difficult problem, but the students were encouraged to carry
on.


July-September 2009: The students successfully developed a core set of ideas to
connect dynamics of regulatory systems in the cell to the sentence parsing
algorithms. Based on these ideas, they developed a mathematical model which
was formulated as a large set of ordinary differential equations. They later used
the model to demonstrate that it works.


October 2009: Four members of the team participated in the iGEM ‘Jamboree’
(an international final attented by 500 students, many from top-ranking
universities). For their efforts, the Gothenburg team (called Sweden) were
awarded with a shared bronze medal.

In summary, we think this first participation in iGEM was very successful, and
think the training value was high. We recommend future participation in iGEM,
and identify the following suggestions for future improvements


1) Teachers should be more active in forming teams. At leading universities
iGEM is identified as a prestige competition and attracts the very best students.


2) To enable experimental work and attract students, the iGEM should be
equipped with a support package of e.g. 100 kSEK budget for experimental
work, and funds for 4 students to attend finals, and some form of lab space.


Sven Nelander
Assistant Professor at Wallenberg Lab Sahlgren´s Academy


Student perspective and learning experience of the iGEM team

The iGEM competition gave the students a great opportunity to try something
new and different and to work independently. It was the opportunity to develop
and implement a poject and also to present it in Boston at the jamboree that
drove the formation of the team. The jamboree gave the possibility to meet
researchers and other students from all over the world and to present your
project t to them, Apart from the 20 minute presentation we had to hold a poster
reception. During this reception you had the opportunity to go to the projects
which interest you and ask questions to the teams.

To develop the project of sentence parsing bacteria we were able to integrate our
previous knowledge into the synthetic biology context. Starting from
computational linguistic and transforming the mathematical model into a
biological model. This gave an opportunity to apply the things you learned in
class to a problem you have chosen on your own.

On top of the knowledge we gained we also enhanced our abilities in soft skills.
We had to work in a team with different backgrounds and nationalities and we
had to handle differences without letting the team fall apart. We improved our
organizational skills as well. We had to divide the different tasks within the
group and had to organize plane tickets and the hotel for the jamboree The
iGEM experience was also a opportunity to gain performance skills.

Anna Hallerbach
Master student in MPBIS, Chalmers

								
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