2. Point-by-point comments
Major achievements
Strong development of projects with clinical usefulness
Excellent external grants more than doubled
Number of publications increased by 69%
Number of publications in high impact journals more than tripled
Number of interfaculty publication almost doubled
Strong external recruitment of new group leaders
Postdoctoral program developed
Technical platforms established Clinical usefulness of the research
The strategic research area (SRA) has undergone extensive expansion, both with respect to the number of group leaders and funded research projects, as well as the size of the
funding. In accordance with this greatly increased activity, a large number of projects with clinical applications have been undertaken. These include, but are not limited to the
following (see also attached Impact case studies), with the numbers relating to the goals set up in the contract for the SRA:
1. Developing and clinically evaluating new techniques for quantifying the demyelination process in neurological disease: A quantitative MRI method, which produces maps of the myelin content of the brain i.e. a quantitative measure of the volume proportion of myelin in each pixel, has been developed (Warntjes et al., 2010, 2011a, b).
2. Establishing reliable examination paradigms for assessing chronic pain sensitivity and for localizing language function with fMRI: Work with fMRI paradigms for assessing language localization has resulted in examination routines that have proven reliable and have been tested in clinical examinations (Ettinger-Veenstra et al., 2010, 2012; Engstrom et al., 2010). 3. Developing and evaluating tools for navigation and improved resection in brain tumour surgery and for the implantation of deep brain stimulation electrodes: For the segmentation of the brain and brain tumours, methods based on quantitative MRI and level sets have been developed (Warntjes et al., 2009; Wang et al., 2013). To enable deformation in real time of preoperatively acquired MRI images to fit the current anatomy, we have developed a pipeline for following the brain shift by identifying vessels, visible both with optical cameras and in the MRI data (Marreiros et al., 2013a, b).
4. Developing surrogate biomarkers for imaging or neuropsychiatric disease: Not yet achieved, but work is ongoing in the areas of diffusion MRI and MR spectroscopy.
5. Developing fluorescent probes for detection and characterization of amyloid protein in neurodegenerative disease: Poly-thiophene probes (LCO/LCPs) have been developed for imaging of in vivo produced amyloid-beta and or Tau aggregates of various morphotypes in models of Alzheimer’s disease (Wegenast-Braun et al., 2012; Heilbronner et al., 2013; Nyström et al., 2013).
6. Developing improved drug screening animal platforms for neurodegenerative disease: By improved genetic engineering, the Drosophila (fruit fly) system has been developed into a system for genetic and compound testing of candidate proteins and molecules involved in Alzheimer’s disease (Caesar et al., 2012).
7. Identifying novel drug targets for the treatment of inflammation-related brain-elicited disease symptoms: The mechanisms of immune-to-brain signalling have been examined, with
the identification of critical signalling molecules (Hamzic et al., 2013; Ruud et al., 2013; Ihnatko et al., 2013).
8. Identification of key candidate genes involved in the development of OCD- and anxiety-related behaviour in chickens, which can serve as models for human diseases: Using a novel combined approach of QTL- and eQTL-mapping, and overlaying with known selective sweeps, we have identified a number of candidate genes for anxiety related behaviour. 9. Treatment of epilepsy: We have found and detailed a potential antiepileptic mechanism where lipophilic and negatively charged compounds open some K channels. Currently, we are synthesizing 10 new compounds per month, which we screen against a specially designed K channel to selectively pick promising compounds. These compounds will be tested in a brain slice epilepsy model (Börjesson et al., 2010, 2011; Tigerholm et al., 2012).
10. Developing methods for delivering protective estrogen to the diseased brain: We have studied and validated different methods for administering estradiol to rats and mice showing that the most commonly used commercially available method results in supraphysiological and neurodamaging concentrations (Ström et al., 2010, 2013a, b). We have furthermore validated a convenient and low cost method for parenteral administration and invented a new method for enteral administration in order to cater for the liver metabolism (Ingberg et al., 2012; Ström et al., 2012).
In addition to progress within these ten specific clinically oriented projects, it should be noted that a substantial part of the research with the SRA is carried out at the Institute of Technology, and therefore extends beyond human medicine. A major part of this research instead deals with animal behavior and welfare. This work may still have profound societal importance, since it relates to important aspects of animal husbandry in food production. As an example hereof, research carried out on long-time and trans-generational effects of early experiences is important for understanding how animals are tuned to cope with environmental stress, and may lead to new recommendations regarding rearing and breeding. Furthermore, some of the investigated genetic and epigenetic effects will likely prove to be relevant also for humans, and may thus in the long-term generate clinically relevant results.
External grants
The total number of external grants, as well as the number of “excellent” grants, that has been awarded the PIs of the SRA as main applicants, has almost doubled, and the sums received have more than doubled. During 2013 the total number of projects supported by external grants was 46 (26 for 2008/2009)i. The number of “excellent” grants was 30 (16). For 2013, 45 million SEK (24) has been received, out of which 38 (16) has been from “excellent” grants. Part of the large increase is due to grants given to newly recruited group leaders (“Recruitments”), but also among the 8 original principal investigatorsii the
number of grants and sums received have increased. For these original principal
investigators, a total of 29 grants have been awarded for 2013, out of which “excellent” grants are 20. A total of 29 million and 24 million, respectively, have been received. The increase in this group alone was thus 12% and 25% for number of grants and number of
i All grants available during 2013 are included i.e., both new grants with starting date during 2013, as well as
“guaranteed” grants for 2013 awarded a previous year. Note however that we have only included grants awarded to an SRA member when they are an employee of Linköping University. Hence grants awarded to newly recruited PIs when still at their previous academic institution are not included.
ii One of the original PIs has left the strategic area. However, starting figures, for the years 2008-2009, include
excellent grants, respectively, and 21% for the sums received in external grants in total and an impressive 50% for excellent grants. Notably, one of the senior PIs (Per Jensen) has been rewarded an Advanced grant from the European Research Council, and two of the junior PIs (David Engblom and Peter Nilsson) have received ERC Starting grants. Another senior PI (Stefan Thor) has been rewarded a major Wallenberg Foundation grant and has become a Wallenberg Scholar.
Interfaculty grants have increased from 4/year and 7600 million to 9/year and 8900 million for 2013.
Considering the increased competition for external funding, the SRA has been extremely successful. Part of this can be explained by the strong emphasis among the major granting agencies on the most promising young scientist, several of those being found among the newly recruited. However, also the established, more senior scientists have increased their funding, being a sign of competitiveness. With the present strong focus among decision-makers on support for “excellent” research it is of utmost importance that the successful group leaders within the SRA can maintain a very high standard of their research. A critical fact is, obviously, adequate financial support. Because of previous allocations of large grants to certain research environments nationally, but not to life science at LiU/LiÖ, many of the leading scientists at other universities with which SRA members are competing, have means at their disposal that are several-folds larger than what is available, even for the top funded investigators within our SRA. Decisive support, also in terms of direct additional funding from the University/Faculty and County (LiÖ), is therefore necessary to bridge this gap.
Publications
The number of publications has increased by 69 %. Thus, during 2013 so far in average 62 papers have been published, to be compared with 36/year for 2008/2009. The number of publications in high impact journals (IP >5) has more than tripled, from 5/year till 17 during 2013 so far. It should be noted that the figures for the present year are based on 10-11 months only, and hence are likely to increase still furtheriii. While a large part of the
increase in the number of publications can be ascribed to new recruitments (see below), also among the original 8 principal investigators the number of publications, particularly in high impact journals, have increased considerably, i.e., more than doubled.
There has been increased co-operation across faculties, e.g., Elinder-Konradsson, Thor-Hammarström, Kågedahl - Brorsson, and Smedby - Ynnerman. This is reflected by the number of interfaculty publications which has increased from 3.6/year, during 2005-2009, to 6.5/year, during 2010-2013.
We feel that the figures are impressive, considering that it has become increasing more difficult to publish, especially in high impact journals. It is now generally required that the scientific question in question must be addressed from a large number of aspects and with several different methods, and, especially for basic science, that the work is functional, not descriptive. This places increasing demands on the research groups, requiring both a critical volume and access to an extensive methodological arsenal. The SRA has taken measures to meet such demands by e.g., creating a post-doctoral program, by which the research groups can recruit already educated scientists who may also bring in
iii Note that only publications with Linköping University in the address line have been included; hence
new methodological know-how, and by building common technical platforms, to thereby ensure that the research groups have access to state-of-the methodology also outside their own expertize. In addition, the SRA has allocates resources for the acquisition of new equipment critical for ongoing research projects (see “Budget”).
Citations
The number of citations to publications by SRA research leaders have increased, from in average 1700/year to about 3100 for 2012 i.e., an increase of 83%iv. Among the original PI’s the number of citations was over 1800 for 2012, suggesting that the number of citations has remained about the same for this group.
Recruitments
New group leaders. The SRA has shown a strong increase in the number of independent group leaders. This is largely due to a high success rate among neuroscientists in achieving LiU-Foass and LiÖ “Foass” positions (junior investigator positions). In fact, one third (8 out of 24) of all LiU-Foass positions (all Faculties), and one of four LiÖ “Foass” positions, have been awarded to neuroscientists. Out of the 9 independent group leaders thereby recruitedv, 6 have so far been promoted to senior lecturers. Moreover, the SRA has also seen the addition of two externally recruited professors (one in “Neuroscience” and one in “Neuroanatomy”vi), and two senior lecturers (one from a regular Foass-position, and one from abroad) i.e., in total 13 new group leaders. A professorship in clinical neurophysiology is furthermore under appointment, with a very strong external candidate.
Postdoctoral program. With the goal of strengthening the research environment, the SRA has launched a postdoctoral program. These positions have been announced in leading
international journals (Nature, Science) with the intension of attracting applicants from abroad. The program has been open to all group leaders of the SRA, including the more junior group leaders, and the main selection criteria have been that the postdoc should be an external recruitment and have scientific merits that would strengthen the host research group. The recruitment has thus been stringent, to thereby ensure a high scientific standard. Support from the SRA has come in the form of 50% of the salary/stipend cost for the postdoc for two year, with the possibility of extension for another two years. So far, 12 postdoctoral fellows have joined the program. Many of the fellows have been from abroad (Denmark, Germany, UK, Italy, Slovakia, Japan, and USA).
Support to clinical research. As will be detailed in the document describing future directions of the SRA, we feel that one of the urgent measures that need to be taken is to strengthen clinical research within the neuroscience field. As one initiative we have therefore allocated means (1.5 Mkr) specifically for clinical researchers to be used for their own salaries to provide time for research (“forskarmånader”). To a large extent these means were allocated to young clinicians working on their PhD-thesis. Furthermore, the creation of technology platforms (see below) is another implement that will help support clinical researchers, as well as increase the interactions between preclinical and preclinical research in that it gives them access to methodology which otherwise would be difficult to achieve.
iv Note that the figures are compilations of the citations to each group leader. This implies that in case of
citations to collaborative studies among group leader, citations to the publications in question may have been counted more than once.
v 5 were appointed on their position before the starting date of the SRA vi Appointed; starting date January 1, 2014
Technology platforms. To facilitate use of techniques and equipment with which the
individual research group may not have detailed knowledge, the SRA has created technology platforms, run by an expert laboratory engineer with a PhD degree. A total of 6 platforms have so far been established: small animal behavior, electrophysiology, microdialysis, proteomics, synthetic chemistry, and magnetic resonance imaging. To ensure a continuously high standard, about a third of the engineer’s time is set free for his/her own, preferentially, technically oriented research. Each platform and platform manager is supervised by a member of the SRA that has expertise in the field. We feel that this organization is a preferred way to facilitate methodological co-operation between research groups, without placing the strain of the individual group to devote time and money on projects that may be outside their own research interest. Notably, the technical platform in magnetic resonance imaging will also strengthen the collaboration between the SRA and CMIV.
Organization of PhD supervision
The number of students with supervisors from two faculties or clinical and basic science has remained at a high level, and at present 9 students (16%) have supervisors from two different faculties or have supervisors from both clinical and basic science.
To stimulate graduate education, the strategic area has launched a program that provides financial support to each group leader that has passed a graduate student to licentiate examination or half-time control. In addition, as detailed above, we also provided means specifically directed to clinical researchers, which primarily became allocated to young clinicians working on their PhD-thesis.
Organization of management and administration
The strategic area is run by a steering group, consisting of eight of the original PIs, one of the newly recruited professors, and one representative for the junior faculty. Chairperson for 2010-2011 was Fredrik Elinder. When he was appointed vice Dean for the Faculty of Health Sciences, Anders Blomqvist took over as chairperson, effective by 1 January 2012. The steering committee meets monthly. Administrative assistance is provided via the host department, including a part time secretary and financial administration.
Budget
Investments in technology platforms include: a microarray station, two confocal microscopes (at Valla and HU, respectively), equipment for fMRI and MRS, for behavioral studies, for capillary electrophoresis combined with mass-spectrometry detection, and for optical coherence tomography.
Linköping, December 6, 2013
Anders Blomqvist Professor, Chair
