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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