R&D Institutions

Resultado da avaliação 2007 na área de Ciências da Saúde

Unidade de I&D

Instituto Biomédico de Investigação de Luz e Imagem - IBILI [HESC-Centro-Coimbra-3282] visitada em 01/02/2008

Classificação: Excellent

Comentários do painel de avaliação
Sobre a unidade
The core of the Unit has been the research carried out in the field of the visual system, in particular in ophthalmology with a strong emphasis on diabetic retinopathy and macular degeneration. The leading position of this Unit is recognized internationally. This Unit has a long tradition of high quality research and, by way of AIBILI, is an important partner of the Integrated Project Functional Genomics of the Retina in Health and Disease. More recently the Unit was strengthened considerably with new research lines that are at the forefront of the field of the cognitive neurosciences particularly with respect to the visual system. Furthermore the Unit has acquired a strong position in the field of imaging methodologies both at the level of the retina and the brain, and it occupies a central position in this important field of science in Portugal. The Panel was very satisfied that the question of the succession of the historical leader, Prof Dr Cunha-Vaz who is about to retire, has been solved in a very positive way with the appointment of the highly esteemed scientist Prof Dr Miguel Castelo-Branco as the new Unit leader. Without questioning this excellent choice one may argue that important appointments such as this one should preferentially be realized through the process of an open competition as done in many advanced foreign institutions. This should be the standard procedure in the future.

The Unit, in general, should take the opportunity of this evaluation and of the changing of leadership to reassess its internal organization. As stated below some reorganization with the formation of a smaller number of larger groups around a common focus, possibly combining complementary approaches would strengthen the efficiency and visibility of the research lines. A number of specific comments, suggestions and recommendations are given below in the reports concerning the different research groups.
The Panel identified in this Unit at least two groups that are very good to excellent while most others did high quality international research that should be classified as very good.

Sobre os grupos de investigação
Ageing and Molecular Mechanisms of Diseases (RP2.B) [RG-HESC-Centro-Coimbra-3282-1187]
This group has a valuable contribution in the field of age-related mechanisms leading to pathological retinal conditions, in particular through the ubiquitin-proteasome pathway (UPP). Furthermore the group has revealed important aspects of the disturbances of signal transduction and the intercellular communication in retinal cells, and in lens epithelial cells.
The focus of this group is on molecular mechanisms underlying Macular Degeneration (MD) and Diabetic Retinopathy (DR), and in particular on the UPP pathway. We should note that the group appears to plan to work, apart from in the UPP system, also in the lens and the retina, and on the roles of glutamate ATP, HIF, neuropeptide Y, oxidative stress and inflammation. Clearly, with the increasingly knowledge of the complex molecular and cellular mechanisms underlying MD and DR, more focussed research is needed if one wants to continue to compete at the international level.
A more specific remark should be made concerning the focus on the UPP system in several cell types in the retina related to MD and DR. This is in principle a good choice, although this system is probably not a causal factor for these diseases, but rather a more general defence mechanism of the cell when something goes wrong at the molecular level. Nonetheless, the differences and similarities in the UPP defence mechanism in different retinal cells is of interest for the progression of both DR and MD, and therefore useful. The choice of studying (the effect of) a target like HIF-1 is appropriate, if carried out with enough thrust, i.e. with sufficient critical mass.
A number of publications, particularly those where the degradation of the ubiquitin-proteasome pathway is described have appeared in journals with a relatively high impact. Two M.Sc. theses were completed. No PhD theses are mentioned.
We recommend that this group should benefit by hiring one or more geneticists, molecular and/or cell biologists, which could introduce transfection techniques of molecularly modified constructs in retinal and endothelial cells and animal models (for MD and DR) to study the functional effect of very subtle or specific (gene) changes. The ability to study structure and function seems already largely present in the group (microscopy and electrophysiology). An upgrade of the confocal microcope seems reasonable.
Diabetic Endothelial Dysfunction (RP2.D) [RG-HESC-Centro-Coimbra-3282-1190]
The group has identified novel mechanisms showing that glycolytic intermediates may be responsible for the loss of tissue response to hypoxia resulting in cell death and tissue damage. In particular they demonstrated that methylglyoxal (increased in diabetes) may disrupt cell response to hypoxia, leading to apoptotic cell death. This group has well established expertise in animal models of diabetes and in diabetes-associated phenotypes not only in the in retina but also in other organs such as kidney, heart and brain.
This group and that of Paulo Pereira appear to be very close in terms of methodology and objects of research. We wonder why these two groups are separated. In the future it would be beneficial to join related small groups, like these two, in larger groups that have a common and complementary objectives and very similar methodologies.
The report does not mention Theses (PhD, MSc) realized in the period being assessed, but it should be noted that the group appears to have started officially in 2007.
As stated for the group of Paulo Pereira this group should also benefit from further integration of molecular biological techniques in its research programs.
Functional Studies of Drug Action at Systems Level (RP2.C) [RG-HESC-Centro-Coimbra-3282-1189]
The main activity of this group consists in the investigation of the role of methamphetamine and/or morphine on acute changes in dopamine transmission and neurotoxicity. The group has collaborated with different groups particularly of the Center of Neurosciences of Coimbra (CNC) and has published together with scientists from CNC. Most publications, however, are in journals of moderate or low impact.
The relevance of this research line to the whole of activities of the Unit is not strong. A more direct involvement in pharmacological studies of neurotransmitters systems in the retina and visual pathways, such as monoaminergic systems, would enhance the relevance of this group in the context of the Unit and might lead to develop novel opportunities. Otherwise the group may be advised to find another organizational basis for continuing the same research line that has been its main focus in the past. In the present situation the group appears to be rather isolated from the rest of the Unit and does not belong to the core of the Unit
Molecular Imaging of the Brain in Ageing (RP1.B) [RG-HESC-Centro-Coimbra-3282-1667]
This group is a relatively small group within the research unit. Related to its size, the group has a high scientific output. The track record of the P.I. is excellent.
The aim of the group is focused, but also limited: To perform Molecular imaging using PET-PET-CT, and SPECT in multi-modal studies of normal and pathological aging of the brain. The PI has contributed to important discoveries, namely with respect to the elucidation of the role of dopamine transporters in dementia with Lewy bodies and Parkinson disease.
The research of this group can have an important impact in the scientific activities of the whole Unit with the development of advanced imaging techniques: PET, SPECT among others. The facilities are being built and we may hope that they will be operational within months. Surprisingly this group has not supervised theses. A stronger contribution to teaching would be most appropriate to consolidate and refresh the group, and to increase its visibility. We wonder whether the size (critical mass) of this small group itself (not counting input form other groups) is large enough to maintain its current output. The formation of active crosslinks with other groups within the Unit and clinical groups should be recommended;
Excellent track record of the PI.
New Methods Of Functional Imaging in Retinal Diseases (RP1.C) [RG-HESC-Centro-Coimbra-3282-1668]
This group is mainly focused on the development of methodologies and techniques. Main achievements have been obtained regarding the development and application of dual wavelength confocal laser scanning ophthalmoscope for in vivo measurement of macular pigment density.
The number of patents in the last four years is impressive (4) and shows that, in this small group, creativity is coupled with expertise in physics and ophthalmological techniques.
The technical advances made by the group resulted in a US provisional patent application, a method for measuring quantity of a fluorochrome in a biological environment (November, 2006); a dual wavelength confocal laser scanning ophthalmoscope for in vivo measurements (September, 2006); a corneal confocal microscope for mapping corneal fluorescence (2005) and a new solid-state ocular fluorometer for measuring blood-ocular barriers permeability (2004).
In contrast the group has a very modest amount of publications in peer reviewed journals and the bibliometric record of the PI is also quite modest. Nevertheless the group delivered one PhD thesis and one MSc thesis in the period assessed. Clearly the contributions of this group should be made more visible in the form of scientific publications in important journals of the field.
Phenotyping Degenerative Diseases of Retina and Optic Nerve (RP2.A) [RG-HESC-Centro-Coimbra-3282-1186]
This group has a long tradition of high quality research in the field of ophthalmology with a strong emphasis on diabetic retinopathy and macular degeneration, but also some lens and glaucoma research is carried out. The leading position of this group is recognized internationally and, by way of AIBILI, is an important partner of the Integrated Project Functional Genomics of the Retina in Health and Disease (EVI-GENORET). Although the group has not published much in journals of high impact, it has a steady number of publications in very good specialized journals. In the period evaluated the group has produced one PhD thesis and 3 M.Sc; this is a fair share in the total of the entire research unit. However, it should be noted that the total number of PhD’s en MSc’s for the entire research unit is rather low.
Furthermore the group has produced important methodological and technical advances with respect to the identification of macular oedema and to the measurement of retinal leakage. It is advisable for this group to explore actively the research lines leading to the description of phenotypes in quantifiable ways, and to obtain non-invasive, higher resolution images of pathology to allow the establishment of clear links between the clinic features and the corresponding molecular and cellular processes.

The group has patent applications, and participates actively in various drug trials. Furthermore the group has made important contributions to international clinical trials (in addition it has carried out contract research with industry regarding drug trials) and plays a leading role in international organizations. A strong point of this group is their leading position in large international collaborative efforts, which are frequently essential not only for clinical trials, but also for genotype-phenotype relationship studies. On the whole the group has a clear plan to continue the development and validation of clinically relevant biomarkers of different kinds of retinal degeneration. In the presentation of the group it should be made clearer which researchers/clinicians have primarily a clinical task, and which have primarily a research task.
The EVI-GENORET network is an excellent achievement to standardize clinical research across Europe. For common diseases, national collaborations can be also, or even more, efficient. The research group could play an important role in setting up a national program to promote ophthalmologic research of a high level with a strong translational dimension.
Another aspect that the group should take into consideration is the organization of clinical genetic databases in order to optimize patient care, clinical trials, genetic counselling and research, as well as the necessary bioinformatics support.
An issue of concern regards the fact the Professor José da Cunha-Vaz will retire shortly. During the site visit we were told that the Unit is taking care of the succession adequately and the he will stay in the direct environment of the Unit due to his position as director of ABILI.
Tools for Clinical Imaging and Technology Transfer (RP3) [RG-HESC-Centro-Coimbra-3282-1192]
The group is mainly focussed on methodological and technological issues related to signalling pathways in the field of oncology. The group could benefit from the rest of the Unit much more, and reciprocally the Unit could benefit from this group more, if the group would carry investigations more related to the main topics of the research lines of the Unit.
We may suggest, within the current setting, to shift the focus of this group to the investigation of neural and retinal tumours.
Although the group is primarily technologically driven it does not appear to have generated patents or contract research with Industry, as yet. Such activities should be encouraged.
Within the group a considerable number of PhD (2) and M.Sc. (5) theses were completed what is a considerable achievement. The scientific output of the group, if placed in the context of the (international) oncology field, is average, and should be improved over the next period. The goals set out by this group are quite heterogeneous, partly due to the focus on developing technological applications, rather than primarily on scientific questions or mechanisms of disease or function. We consider that the existence of a group like this one can be justified within this research Unit, on condition that it clearly interacts with the other groups in terms of science and technology.
Visual Neuroscience Laboratory (RP1.A) [RG-HESC-Centro-Coimbra-3282-1579]
The scientific output of the group is excellent as compared to international standards. Several manuscripts in high-impact journals have been published over the last 5-7 years. The external funding rate is relatively good. Furthermore, the group is embedded in several large national and international collaboration networks addressing primarily retinal and brain imaging. The research line is at the forefront of the field of the cognitive neurosciences particularly with respect to the visual system. The group delivered 1 PhD and 3 master students.
The future objectives are aimed at retinal signalling and retino-cortical processing. These are excellent and timely objectives, although the integration with the genetic or molecular component of these studies is not strongly defined. The (current) genetic and molecular expertise within the group is low. We suggest that the group considers this issue and establishes stronger links with other groups with this expertise.
The research line could be enhanced by collaboration with groups specialized in (human) genetics or ophthalmogenetics, to image retina’s and brains of individuals with defined genetic disorders.
Our only concern regards “feasibility”, due to the little visibility of the Portuguese group of collaborators. Indeed many Ph D members of the group don’t appear to have contributed much to the productivity, as yet. One set of papers is written with the German colleagues from Frankfurt and another with the Dutch from Maastricht, but many of the names of Portuguese members of the group, with a few exceptions, do not appear on the lists of the more recent papers.
The feasibility would improve considerably if the required Technician for Brain Imaging Experiments, the PhD Student in IT, and mainly the PostDoctoral Fellow in MR Physics would be awarded, to stimulate the further development of imaging methodologies (Image and signal processing in retinal and brain Imaging based on pulse programming). This is an important priority. Since the group is participating, and even leading the National Network on Brain Imaging some of the necessary expertise in the domain of specialized physics and imaging technologies might be obtained in the form of programmatic collaborations.
For the brain imaging part in particular, considerable amounts of funds are needed to buy, develop and maintain advanced equipment and to attract and keep dedicated personnel to rise to, or stay on, the top of this exploding field. The inherent costs to maintain this high level research and the expensive maintenance costs of MR experiments (Helium supply) should be taken into consideration by the FCT.

Comentários da unidade

A direcção do IBILI vem por este meio congratular-se com o rigor do processo de avaliação da FCT, e pela classificação obtida de Excelente, que para além do estímulo e da responsabilidade associadas, cria também novas exigências para a Unidade.
Congratulamo-nos com o apontar dos pontos fortes, mas também com a ênfase objectiva nos pontos que podem e devem ser melhorados. Facilitou neste aspecto a metodologia seguida de efectuar uma análise criteriosa da produtividade de todos os grupos científicos, e nas recomendações explícitas para a melhoria. Em traços gerais, estas salientam um investimento claro no mérito e a focagem de objectivos num número reduzido de linhas de investigação e áreas de excelência.
Como único ponto negativo salientamos apenas o lapso de cerca de 10 meses entre a avaliação e a divulgação dos resultados, e se nos apraz verificar que alguns dos pontos em que foram feitas sugestões de melhoria foram entretanto reajustados, teria sido mais eficaz operar algumas das sugestões no imediato.
Aproveitamos finalmente para agradecer as ferramentas e directrizes criadas pelo próprio processo de avaliação, bem como as sugestões de investimento programático, que nos vão permitir tentar melhorar ainda mais a produtividade e competitividade da nossa Unidade.