Download Name of fellow:

Career Development Plan-Year 1
Name of fellow:
Martin Zehl
Department:
University of Southern Denmark
Department of Biochemistry and Molecular Biology
Protein Research Group
Name of Supervisor:
Ole Nørregaard Jensen
Date:
01/10/2006
BRIEF OVERVIEW OF RESEARCH PROJECT AND MAJOR ACCOMPLISHMENTS EXPECTED:
Mass spectrometry (MS) plays an important role in the post-genomic era due to its power for
protein identification as well as characterization of the primary structure and posttranslational
modifications of proteins. The detailed study of noncovalent interactions between
biomolecules by mass spectrometry is also a field of growing interest, but still far from being
routine. Especially the investigation of temporary and/or substoichiometric assemblies is a big
challenge. In order to develop general, sensitive mass spectrometric methods for the study of
such protein-DNA interactions, two different techniques will be applied:
(1) UV-induced cross-linking of proteins to nucleic acids followed by detailed structural
analysis of the conjugated protein to localize the cross-linked amino acids and thereby
identify the nucleic acid binding site. Although the feasibility of this approach has been
shown in the past, significant improvements are required in order to enhance the sensitivity of
this method. This should be achieved by an increased UV-cross-linking yield, new enrichment
and purification strategies as well as the application of state-of-the-art MS instruments.
(2) Hydrogen/deuterium exchange MS in order to obtain information about the whole proteinDNA interaction interface and to study structural transitions of proteins upon DNA binding.
This technique is well established for protein-protein interactions, but has to be adapted for
the study of protein-nucleic acid assemblies.
Following the development and optimisation of the MS-based methods to study protein-DNA
interactions, they will be applied to the (restriction) enzymes under study by the cooperation
partners in the research training network. A significant contribution to the understanding of
the investigated proteins and their functions, and, thus, to the basic mechanisms of proteinDNA interactions, can be expected.
LONG-TERM CAREER OBJECTIVES (over 5 years):
1. Goals: To become an established scientist in the field of biological mass spectrometry,
with a focus on the application of mass spectrometry to the investigation of
biomolecular interactions. This should enable me to obtain a job as a scientist in a
well-known research laboratory, either in an academic or in an industrial setting.
2. What further research activity or other training is needed to attain these goals?
o To plan and undertake a three-year programme of laboratory-based research,
developing and applying MS-based methods to study protein-DNA, proteinRNA and protein-protein interactions in detail.
o To publish the results in high quality, peer-review international journals
o To participate in international conferences, focused on mass spectrometry or
proteomics, is important to stay up-to-date with the recent developments in this
field and to come in contact with potential employers (academic and industrial
institutions).
o To develop and maintain cooperative networks and collaborations, which
should persist for longer than the three years of my appointment in the network
SHORT-TERM OBJECTIVES (1-2 years):
1. Research results
o Anticipated publications: After an approximately 1-year period dedicated to
the establishment of Two or more methodological articles, describing
improvements in the mass spectrometric analysis for the investigation of
protein-DNA, protein-RNA and protein-protein interactions. The application
of these methods to the enzymes under study by the cooperation partners in the
research training network should result in several collaborative papers in life
science journals.
o Anticipated conference, workshop attendance, courses, and /or seminar
presentations: The above-mentioned results will be presented at the annual
meetings of the DNA:enzymes RTN as well as at other conferences,
workshops and courses, mainly those focused on mass spectrometry or
proteomics. The participation in at least one “big” conference and one smaller
conference or meeting per year is anticipated (to be identified when
advertised).
2. Research skills and techniques:
o Training in specific new areas, or technical expertise etc: In general, working
in the Protein Research Group at the University of Southern Denmark will give
me the opportunity to broaden my knowledge and improve my skills in
biological mass spectrometry and protein chemistry. Particularly, I will work
with several techniques that I have not used before, e.g. UV-induced crosslinking of proteins to nucleic acids, hydrogen/deuterium exchange mass
spectrometry, electron capture dissociation, Fourier transform mass
spectrometry, affinity enrichment methods. Furthermore, participation in the
specialized network-wide workshops in Warsaw will provide training in
bioinformatics.
3. Research management:
o Fellowship or other funding applications planned (indicate name of award if
known; include fellowships with entire funding periods, grants written/applied
for/received, professional society presentation awards or travel awards, etc.)
Applications for travel awards to conferences and meetings will be submitted
when possible.
o Assistance in the planning and execution of a network-wide workshop and
visits from researchers from partners´ laboratories will improve my research
management skills.
o The size of the Protein Research Group (about 50 people) and the high
turnover of students requires every member, but especially those that are more
experienced and stay for longer time-periods, to actively contribute to the
management and organisation. This includes maintaining lab space,
instruments, equipment, and materials, mentoring students and new group
members and detailed planning of the experiments to facilitate an optimal
exploitation of the instrument time.
4. Communication skills: Working in an international research group and participating in
an international research training network will markedly improve my English. The
multidisciplinary nature of the network will require to communicate knowledge from
one’s own field to non-experts and the preparation of collaborative, multidisciplinary
journal articles will broaden my experience in scientific writing. In order to enhance
my presentation skills, I will regularly present results at my host university, at the
annual meetings of the network and at other conferences and workshops. Furthermore,
I plan to learn Danish as a second foreign language.
5. Other professional training (course work, teaching activity): I will be involved in
teaching by giving lectures at courses and workshops. In addition, I will train and
supervise visiting early-stage researchers from the network and new members of the
Protein Research Group. This training in teaching and transfer of knowledge will be
very helpful for my further career.
6. Anticipated networking opportunities: The development and maintenance of
cooperative networks and collaborations is not only at the heart of the research
training network, but also one of my main personal goals. They will not only be the
basis of excellent scientific results obtained while the duration of the funded project,
but can also be extremely productive and helpful in the following years. This requires
not only participation in the network meetings, but also stays in the partners´
laboratories, and providing help and training to visiting researchers. Particularly,
possible collaborative research projects with the groups in Vilnius (Virginjus Siksnys),
Newcastle (Bernard Connolly) and Giessen (Peter Friedhoff) have been discussed
during the 1st annual meeting of the Marie Curie RTN and will be established in the
following months.
7. Other activities (community, etc) with professional relevance: Participation in
international mass spectrometry conferences is important to stay up-to-date with the
recent developments in this field and to come in contact with potential employers
(academic and industrial institutions).
Date & Signature of fellow:
Date & Signature of supervisor
01/10/2006
01/10/2006