This post highlights the approach and finding of a new research article published by Disease Models and Mechanisms (DMM). This feature is written by Olivia Howell as apart of a seminar at The University of Alabama (taught by DMM Editorial Board member, Prof. Guy Caldwell) on current topics related to use of animal and cellular model systems in studies of human disease.
Within the brain, anomalies in neuronal migration can precipitate aberrant phenotypes such as epilepsy, a disorder in which atypical neuronal circuitry induces recurrent seizures alongside additional neurological abnormalities2,3. X-linked infantile spasms syndrome (ISSX) is one such debilitating epileptic subtype hallmarked by intellectual disability and intractable seizures that first present in infancy4. Previous work has established a causative link between ISSX and mutations in the Aristaless-related homeobox (ARX) – a gene that influences tangential and radial migration of some GABAergic interneurons vital for repressing excitatory neuronal signaling5,6,7,8. Despite recent progress, the precise pathogenesis of ISSX as well as safe, specific and effective treatments remain elusive. Consequently, characterization of early progenitor interneurons is crucial to understanding and managing this disorder.
In this report, Siehr et al. hypothesized that recapitulating pancreatic ARX functionality within a developing neuronal framework would elucidate the role of this gene in ISSX and the means by which E2 and ACTH mediate their anti-epileptic effects7. They therefore utilized an Arx(GCG)10+7 mouse model that recapitulates the ISSX phenotype to uncover temporally increased levels of apoptosis within the neocortex of Arx-mutant mice. Because this abnormal pattern of apoptosis could not be ascribed to ARX cell death, Siehr et al. deemed it non-cell autonomous in nature. While the affected cell population remains unascertained, Siehr and colleagues have definitively eliminated cortical non-ARX expressing interneurons and inflammatory processes from consideration by examining postnatal neuronal survival and neuroinflammation.
In regard to therapeutics, E2 was found to mitigate ARX+ cell density and ISSX seizure phenotype but proved unable to rescue increased apoptosis – rendering the utility of this drug unresolved. Moreover, the unanticipated failure of ACTH to rescue ARX (GCG)10+7 mutants from seizure phenotype may ultimately lay the groundwork to model intractable ACTH-resistant ISSX cases and thereby explore alternative ISSX treatments.
Notably, the authors herein report the first known observation of ARX-associated apoptosis in an ARX (GCG)10+7 rodent model for ISSX – a corroboration of findings in pancreatic tissue expressing aberrant ARX that highlights the relevance of cross-organ systems research. While too soon to conclude that apoptosis contributes to ISSX pathogenesis, these results underscore the broad, varied and lingering effects of ARX upon neuronal structure and development. Accordingly, one can expect that subsequent pharmacodynamic studies of E2 and ACTH may ascertain their therapeutic relevance to ISSX while also elucidating the relationship between ARX-mediated apoptosis and subclinical molecular features of ISSX pathology.
This post highlights the approach and finding of a new research article published by Disease Models and Mechanisms (DMM). This feature is written by Joseph I. Kaluzny as apart of a seminar at The University of Alabama (taught by DMM Editorial Board member, Prof. Guy Caldwell) on current topics related to use of animal and cellular model systems in studies of human disease.
Fibrolamellar Carcinoma (FLC) is a hepatocellular carcinoma that disproportionately affects young patients and is characterized by a fusion transcript, DNAJB1-PRKACA, which acts as a unique molecular driver and is sufficient for diagnosis (Graham et al., 2015). While liver resection and transplantation remain common management approaches (Kassahun, 2016), the lack of available therapy has motivated molecular mechanistic studies of the fusion.
Previous work has shown that the fusion is sufficient to drive FLC tumorigenesis in murine models (Engelholm et al., 2017). In a recent Disease Models & Mechanisms article, de Oliveira and colleagues chose to study the fusion in zebrafish due to their transparent larvae that provide non-invasive live imaging of liver morphology and inflammatory responses (de Oliveira et al., 2020). The researchers used a hepatocyte-specific promoter to overexpress the fusion and establish an FLC zebrafish line. Liver visualization in adults was achieved via outcrossing with a transgenic line expressing agfp-I10a (Fig. 2A in de Oliveira et al., 2020). The livers of 8- and 12-month-old FLC and control fish were resected for standard histopathological evaluation, which confirmed liver enlargement and abnormal hepatocellular architecture in FLC livers (Fig. 2B-C in de Oliveira et al., 2020).
The investigators then sought to determine if overexpression of the fusion caused alterations indicative of malignancy in larval zebrafish. The researchers confirmed hepatomegaly 7 days post-fertilization, suggesting the potential for zebrafish larvae to be used as a model to study the progression of early FLC, an area of interest for a progressive condition that primarily affects young patients (Fig. 3 in de Oliveira et al., 2020). Overexpression of the fusion increased neutrophil and macrophage infiltration into the liver, TNFα-positive macrophages, and caspase-a activity, confirming an inflammatory response in FLC larvae (de Oliveira et al., 2020). Targeting this inflammation with TNFα and caspase-a inhibitors limited FLC progression.
Despite this potential for therapy, there are many outstanding issues with the zebrafish FLC model, such as the presence of two fusion forms due to the genome duplication in zebrafish, the lack of fibrosis markers characteristic of human FLC progression (Kastenhuber et al., 2017), and alternate pro-inflammatory pathways that are unexplored or understudied in the field (Rigutto et al., 2009), which warrant further study.
Graham, R. P., Jin, L., Knutson, D. L., Kloft-Nelson, S. M., Greipp, P. T., Waldburger, N., Roessler, S., Longerich, T., Roberts, L. R., Oliveira, A. M. et al. (2015). DNAJB1-PRKACA is specific for fibrolamellar carcinoma. Mod Pathol 28, 822-9.
Suvimal Kumar Sindhu, Graduate Student @ Indian Institute of Technology Kanpur, Kanpur, Uttar Pradesh, 208016, India Email: suvimal.sindhu@gmail.com
Having joined my Ph.D. programme at India Institute of Technology Kanpur in India, I always witnessed my senior colleagues defending their Ph.D. thesis with panache and grace; for juniors like me such visuals were highly captivating and motivating. During my Ph.D. I trained to manipulate gene expression and analyze its effect on the developing avian brain. Using these skill-set I created additional hippocampus-like regions (a center of learning and memory) in the chick brain, to understand its development in the brain (Sindhu et al., 2019). I proposed a mechanism for correct positioning of hippocampus in the avian brain. After years of arduous and passionate research work, my defense day was scheduled in the evening of April 17th and I was thrilled, for I was ready to experience the joy and accomplishment, a vicarious pleasure experienced through my senior colleagues, and sincerely hoping to match the high standards set by them.
While I was getting prepared for my D-day, the COVID-19 pandemic started to spread in India. Staying in an autonomous and highly secure residential campus, everybody — I know — thought that our work won’t be affected. However, things escalated quickly and in an unprecedented manner, merely two weeks prior to my defense most of the organizations, including my institute, got shut down. COVID-19 took away everybody “reasons for struggle” in life. Now the only possible thing was to “stay at home” and “work from home”. With a broken heart, I came back to my home located in a remote village in the Indian state of Bihar. Amidst all this, I was becoming anxious and restless, my dream to become a Doctor of Philosophy getting delayed till uncertainty. After more than one month of nationwide lockdown, institutions started to conduct virtual academic seminars and meetings. And I got the opportunity to defend my thesis on the last day of the same month – April. I was disheartened as it would not be the same as a traditional thesis defense, which I had always dreamt of, but this was the only option available under these situations.
[Image on request designed by www.hoodnscience.com]
Suddenly I realized that there would be logistical hurdles, and preparation in the absence of supervisor and lab-mates would be challenging. But, I was determined to do this and decided to troubleshoot every aspect of it. Considering the location of my home two major hurdles were there -1) frequent power failure of home supply and 2) unstable cellular-network. Arranging an alternative power source and a Wi-Fi device was not a problem; I was not sure whether the network – which is mostly congested under current situation – would stably transmit data needed to sustain a group video conference with around 50 participants. More importantly, how much data will it consume? – 2GB, 20GB or, 200GB, any number was just a blind guess. To test these conditions a priori, arranging such huge participants that too with a free version of any video conferencing app was just not feasible. I thought of doing a couple of trial presentations to check if my slides are in order and the quality of audio and video are fine. My first mock presentation with my supervisor was quite upsetting; the connection lasted only for 10 minutes as the network was highly unstable. In the second trial, I changed my location within the limited possibilities and that improved the data speed to ~65MBPS. This time my mock presentation lasted for 50 minutes and it consumed ~270MB of data. This was my first experience to deliver a formal presentation online, and hence sometimes I became oblivious of my virtual audience. I had minimized the video thumbnail of participants to avoid cluttering my screen, which was shared with others for the slide show. However, as a trade-off, I lost touch with my audience, and at times felt speaking to myself. This was also due to the fact that to see the entire shared screen running my slide show.
Finally, the D-day arrived, 10 minutes prior to the scheduled time, I signed-in to the Zoom platform and shared my screen; there were ~10 people waiting for my presentation, which eventually rose to 45 people. The connection became unstable; with stuck video and breaking voice, it was a total chaos. I thought my device would not be able to handle the load, and my presentation will have to be postponed. Meanwhile, it was suggested to temporarily turn off only video transmission for the audience except for the oral board members. This idea was quite helpful and I was able to go through my defense presentation as well as discussion, which took around 90 minutes of time. At the end of the session around 1.8GB of data was consumed. Without the slide transition device and laser pointer, it was inconvenient initially, but I adapted to the keyboard and mouse pointer for managing the presentation. To remain in touch with my audience, this time I did not minimize the video of my participants; rather, I kept a few video thumbnails at the corner of my screen. This helped me in remaining aware of their presence and generated a sense of their physical presence.
I had never thought I would defend my thesis this way, but when the whole world is learning a new way to live, I learned a new way to defend and become a doctor under lock down.
(Edited by Sahil Batra, Graduate Student @ Indian Institute of Technology Kanpur, India)
Sindhu S.K., Udaykumar N., Zaidi M.A.A., Soni A., Sen J. MicroRNA-19b restricts Wnt7b to the hem, which regulates aspects of hippocampus development in the avian forebrain. doi:10.1242/dev.175729, Development, 146, (20):1-7
Welcome to our monthly trawl for developmental biology (and related) preprints.
A real monster of a month, May, with masses of preprints uploaded by scientists in various stages of lockdown. Let us know if we missed anything and use these links to get to the section you want:
The floor-plate of His is a non-neuronal electrical conduction pathway
Kalaimakan Herve Arulkandarajah, Guillaume Osterstock, Agathe Lafont, Herve Le Corronc, Nathalie Escalas, Silvia Corsini, Barbara Le Bras, Juliette Boeri, Antonny Czarnecki, Christine Mouffle, Erika Bullier, Elim Hong, Cathy Soula, Pascal Legendre, Jean-Marie Mangin
MEIS-WNT5A axis regulates development of 4th ventricle choroid plexus
Karol Kaiser, Ahram Jang, Melody P. Lun, Jan Procházka, Ondrej Machon, Michaela Procházková, Benoit Laurent, Daniel Gyllborg, Renée van Amerongen, Petra Kompaníková, Feizhen Wu, Roger A. Barker, Ivana Uramová, Radislav Sedláček, Zbyněk Kozmík, Ernest Arenas, Maria K. Lehtinen, Vítězslav Bryja
Multicellular rosettes organize neuropil formation
Christopher A. Brittin, Anthony Santella, Kristopher Barnes, Mark W. Moyle, Li Fan, Ryan Christensen, Irina Kolotuev, William A. Mohler, Hari Shroff, Daniel A. Colón-Ramos, Zhirong Bao
Cell states beyond transcriptomics: integrating structural organization and gene expression in hiPSC-derived cardiomyocytes
Kaytlyn A. Gerbin, Tanya Grancharova, Rory Donovan-Maiye, Melissa C. Hendershott, Jackson Brown, Stephanie Q. Dinh, Jamie L. Gehring, Matthew Hirano, Gregory R. Johnson, Aditya Nath, Angelique Nelson, Charles M. Roco, Alexander B. Rosenberg, M. Filip Sluzewski, Matheus P. Viana, Calysta Yan, Rebecca J. Zaunbrecher, Kimberly R. Cordes Metzler, Vilas Menon, Sean P. Palecek, Georg Seelig, Nathalie Gaudreault, Theo Knijnenburg, Susanne M. Rafelski, Julie A. Theriot, Ruwanthi N. Gunawardane
Mechanochemical control of epidermal stem cell divisions by B-plexins
Chen Jiang, Ahsan Javed, Laura Kaiser, Michele M. Nava, Dandan Zhao, Dominique T. Brandt, Javier Fernández-Baldovinos, Luping Zhou, Carsten Höß, Kovilen Sawmynaden, Arkadiusz Oleksy, David Matthews, Lee S. Weinstein, Hermann-Josef Gröne, Carien M. Niessen, Stefan Offermanns, Sara A. Wickström, Thomas Worzfeld
Modeling human TBX5 haploinsufficiency predicts regulatory networks for congenital heart disease
Irfan S. Kathiriya, Kavitha S. Rao, Giovanni Iacono, W. Patrick Devine, Andrew P. Blair, Swetansu K. Hota, Michael H. Lai, Bayardo I. Garay, Reuben Thomas, Henry Z. Gong, Lauren K. Wasson, Piyush Goyal, Tatyana Sukonnik, Gunes A. Akgun, Laure D. Bernard, Brynn N. Akerberg, Fei Gu, Kai Li, William T. Pu, Joshua M. Stuart, Christine E. Seidman, J. G. Seidman, Holger Heyn, Benoit G. Bruneau
The gene cortex controls scale colour identity in Heliconius
Luca Livraghi, Joseph J. Hanly, Ling Sheng Loh, Anna Ren, Ian A. Warren, Carolina Concha, Charlotte Wright, Jonah M. Walker, Jessica Foley, Henry Arenas-Castro, Lucas Rene Brenes, Arnaud Martin, W. Owen McMillan, Chris D. Jiggins
Mitochondria form contact sites with the nucleus to couple pro-survival retrograde response
Radha Desai, Daniel A East, Liana Hardy, James Crosby, Manuel Rigon, Danilo Faccenda, María Soledad Alvarez, Aarti Singh, Marta Mainenti, Laura Kuhlman Hussey, Robert Bentham, Gyorgy Szabadkai, Valentina Zappulli, Gurtej Dhoot, Lisa E Romano, Xia Dong, Isabelle Coppens, Anne Hamacher-Brady, J Paul Chapple, Rosella Abeti, Roland A. Fleck, Gema Vizcay-Barrena, Kenneth Smith, Michelangelo Campanella
Today we return our interest to human development, focusing on a special blood cell: the macrophage. Produced in multiple, stem cell-independent waves, macrophages colonize the developing foetus early on, forming several tissue-resident populations. This includes the microglia which are essential for brain and spinal cord development. In this paper, the authors looked into macrophage development in the human embryo, drawing parallels to the better-known mouse and zebrafish models.
First of all, they performed single-cell RNA sequencing on blood cells sampled from 8 human embryos across different Carnegiestages (11 to 23). They sampled the yolk sac (where the first macrophage wave arose), head, liver, blood, skin, and lungs; all sites successively colonized by macrophages. The first round of sequencing was performed with STRT-seq and analysed 1231 cells, from which 15 populations could be identified. This included a yolk-sac derived progenitor group (YSMPs) that strongly resembled the established signature for mouse multipotent cells called erythro-myeloid progenitors (EMPs). Notably, YSMPs were almost completely biased toward the myeloid cell fate, as confirmed by in vitro studies. The second round of sequencing using 10x Genomics confirmed the previous results in more than 11,000 cells. The combined STRT-seq and 10x data were used to define developmental trajectories, in order to understand the origin of the tissue-resident macrophage populations.Interestingly, several of these populations seemed to have already initiated their tissue residency genetic programs, as has been observed in the mouse. Although not a lineage tracing study, the authors described a major contribution of yolk sac-derived macrophages to microglia development. Conversely, YSMPs seem to play a secondary role in microglia formation, a result consistent with mouse development.
In summary, this work confirms the high degree of conservation between species, creating a roadmap for macrophage differentiation. Moreover, it is a testament to the maturity of the single-cell transcriptomic field and the accompanying data analysis.
Starting date: To define due to international confinement.
Contact: david.volle@inserm.fr or david.volle@uca.fr
Our lab studies the mechanisms that lead to testicular pathophysiologies such as fertility disorders or testicular germ cell cancers. We are interested in deciphering the impacts of altered metabolism and/or of exposures to environmental molecules on testicular physiology. In order to perform such work, we are using pharmacological approaches combined with specific genetic models such as C. elegans, transgenic mice, or culture cell of tumor cell lines.
The background of the project. The incidence of testicular germ cell tumors (TGCT) has increased in the last decades. TGCT are the most common solid cancers in young adults. Moreover, 10 to 20% of patients have forms that are resistant to treatment. It is thus essential to improve the treatments in order to provide better care to people with cancers that are resistant to current treatments. In addition, patients who received chemotherapy or radiotherapy are at higher risk of developing a second malignant tumor. To answer the question of treatment efficiency, there is a need to better understand the etiology of TGCT, which remains poorly known.
In order to explore the questions of TGCT biology and their sensitivity to chemo-drugs, we have started a new field of research in our team focusing on nuclear receptors, which has been associated with the development of cancers.
Description of the project. To achieve this project, we will use genetically modified mice that are predisposed to TGCT and testicular organotypic culture system. In addition, we will develop single-cell approach to decipher the molecular mechanisms involved in tumor development, aggressiveness, or chemo-resistance. This analysis will be key to study switches of homeostasis and metabolism between normal to tumor cells. Through these models combined with high-throughput approaches (such as RNAseq), candidate will analyze the biology of germ cell tumors (initiation, progression, and invasion) as well as their sensitivity to therapy in order to decipher the roles of targeted signaling pathways. In addition, the candidate will use C. elegans as a powerful genetic model to validate candidates defined in mouse models. This transposition will be useful to develop a new model to study germ cell tumors in regards to the 3R ethical rules. Expected results. The validation of these models will allow us to first extend their use in the context of TGCT biology in order to provide mechanistic connections between selected signaling pathways and TGCT etiology. Secondly, this work should provide new insights for providing novel prognostic markers and potential therapeutic targets.
Candidates. Qualified candidates should be self-driven and highly motivated individuals with an established track record of success, including first-author publications. Experience in cancer biology, developmental biology, reproductive biology, cell, and molecular biology, or related field(s) is desirable. The candidate must have experience in genetically modified mouse models and/or C. elegans biology, cell culture, single-cell and molecular biology techniques (RNAseq, etc.), bioinformatics skills.
For prompt consideration, please email the following items to Dr. David VOLLE: david.volle@inserm.fr
*A one-page cover letter describing areas of research interests and career goals
*Curriculum vitae with bibliography
*Contact information for 3 references
DEPARTMENT OF MOLECULAR, CELL, & DEVELOPMENTAL BIOLOGY DIVISION OF PHYSICAL AND BIOLOGICAL SCIENCES
1156 HIGH STREET
SANTA CRUZ, CALIFORNIA 95064
Postdoctoral Fellow – Neural Circuit Development – Anatomy and Genomics
The Kim Lab at Molecular, Cell, and Developmental Biology Department, the University of California, Santa Cruz is seeking highly motivated and talented postdoctoral research fellows with a Ph.D. degree to join our new and innovative research group.
The University of California, Santa Cruz is one of 10 universities within the prestigious University of California system. MCD department has top-tier neuroscience and molecular biology labs and UCSC with its genomics institute is an undisputed leader in genomics and bioinformatics. Santa Cruz is a wonderful small progressive town on the central coast of sunny California, nestled into mountains that teem with giant redwood trees, approximately 35 minutes to San Jose/Silicon Valley or 1 hour and half to San Francisco Bay.
The Kim Laboratory aims to investigate connectivity, development, genetic identity, and function of neural circuits using mouse cerebral cortex as a model system. Our ultimate goal is to understand the fundamental principle of neural connectivity and its functions in animal’s perception and behavior. We address our questions using novel neural circuit tracing systems with next-generation trans-synaptic viral tracers, mouse genetics, single-cell genome-wide sequencing, and in vivo imaging. My lab is determined to offer excellent research opportunities to advance your scientific career, strong academic interactions and collaborations across the neuroscience and other biology laboratories at UCSC and more. For additional information, please refer to the following webpage: http://www.ejkimlab.com/
We prefer, but not limited to, candidates with expertise in the following areas: (neuro)developmental biology with genomics experiences, mouse surgery and handling related to neural circuit tracing and manipulations, and molecular and cellular neuroscience. Above all, outstanding applicants with strong quantitative skills are strongly encouraged to apply. Interested individuals should submit an application with a curriculum vitae, a brief cover letter including research interests, and the contact information of three individuals who will provide letters of reference to:
Euiseok Kim, Ph.D.
Assistant Professor
Department of Molecular, Cell, and Developmental Biology University of California, Santa Cruz
ekim62@ucsc.edu
The University of California is an Equal Opportunity/Affirmative Action Employer. All qualified applicants will receive consideration for employment without regard to race, color, religion, sex, sexual orientation, gender identity, national origin, age, disability, protected veteran status, or any other characteristic protected by law.
Join our team! The University of Washington Department of Orthopaedics and Sports Medicine is seeking a Postdoctoral scholar in the Musculoskeletal Systems Biology Lab (MSBL) of Ronald Kwon (https://sites.uw.edu/msblgroup/). The lab is housed in the Institute of Stem Cell and Regenerative Medicine (https://iscrm.uw.edu) in Seattle, Washington. This is an NIH-funded position with potential renewal for up to three years.
The goal of this project is to identify causal genes underlying genetic risk for osteoporosis. Our team has identified genetic variants that protect some individuals from osteoporosis, and make others more susceptible to this disease. To identify the causal genes underlying these risk variants, our lab has developed a rapid zebrafish-based pipeline for the prediction of human skeletal gene function. The candidate will use this pipeline to identify novel genes regulating bone biology and which mediate genetic risk for osteoporosis. Projects feature in vivo modeling in zebrafish, CRISPR-based gene editing, next generation phenotyping, and bioinformatics.
About the MSBL
The MSBL has three major research thrusts: 1) genetic risk for osteoporosis, 2) axial skeletal development, and 3) appendage regeneration. Our focus is on taking bold, innovative approaches.
The MSBL believes that diverse experiences and perspectives are mandatory for scientific excellence (https://sites.uw.edu/msblgroup/equity/). We welcome all willing participants – regardless of gender, race, ethnicity, age, disability, sexual orientation, beliefs, or socioeconomic or cultural background – and work to support each other through trust, encouragement, and honest feedback.
What we are looking for
We are not looking for specific experience or skill but rather candidates with a strong interest in our work. We are also looking for candidates with any combination of the following: curious, creative, passionate learners, willing to take risks, and motivated to take on new challenges. Finally, we are looking for candidates who possess excellent communication skills and a strong commitment to diversity.
Qualifications
Applicants must have a Ph.D. degree (or equivalent) in engineering, life sciences, or a related field at the time of start date.
Application instructions
Applicants should send their CV and cover letter to ronkwon@uw.edu.
Currently, bioinformatics is playing an increasingly important role in life science research. Biologists, clinicians and biomedical researchers have become more dependent on bioinformatics outcomes. Despite the crucial role of bioinformatics in accomplishing multidisciplinary projects, collaborations between biologists and bioinformaticians encounter several difficulties. Here, I outline different types of collaborations and provide an overview of how the relationship between bioinformatics and life science experts can be facilitated.
Potential means of collaboration
Several options for collaboration are available to research groups. Depending on resource availability, they can hire their own bioinformaticians, collaborate with a bioinformatics group within their organization, use the services of an internal bioinformatics core facility, or employ a bioinformatics consulting company outside their organization.
If a bioinformatician is hired by a given research group, all members of the group can have easy access to bioinformatics assistance, communication is easy, and both life scientists and the bioinformatician will feel they have ownership and input into the project, so conflict over assigning credit for output is less likely. However, the work environment might be less competitive for bioinformaticians hired for a specific task because there is insufficient opportunity to expand their expertise, given that they focus on certain types of data related to a specific topic, and there may be minimal constructive criticism from colleagues.
If a research group decides to collaborate with an internal bioinformatics group, creating a good working relationship is more challenging. Bioinformatics groups within academia typically have their own research projects, so their ability to assign time and services to other groups may be limited. Consequently, it is important that resource allocation and expectations should be clearly established and both sides should agree on anticipated credit gains. The risk for bioinformaticians in this scenario is that despite devoting time and expertise to external projects, their contributions might not be valued sufficiently. For example, despite a bioinformatician providing data/results of publishable quality, they may not be assigned a correspondingly prominent position in the authorship list of the resulting scientific papers.
Nowadays, many research institutes have established their own bioinformatics core facilities, with the objective of supporting all research groups in the institute. This could represent an ideal model of collaboration provided that the core facility has a sufficient number of experts, expertise, and resources to tackle the research questions it is presented with. In reality, given the considerable diversity of life science data, newly established core facilities are unlikely to have a sufficient depth of experience to handle all types of data. Accordingly, research groups should be aware of such limitations and must be willing to help core facility bioinformaticians to develop their skills. Where such core facilities are overburdened with requests, there might also be a significant delay in data analysis and revisions.
Finally, outsourcing data analysis by recruiting the services of a professional bioinformatics consultancy is another option, but it appears to be adopted less in academic contexts. Compared to bioinformatics core facilities in academia, professional consultancies tend to be better at project management and generally do not expect authorship rights in publications. However, they are likely to be more expensive, accessibility might be more limited compared to the previous options, and the limitations of core facilities can also be relevant to external consultancies.
Who should sit where?
Bioinformatics is many things. As an interdisciplinary field of science, it has multiple applications including database creation and management, development of software and analytical tools, creation and implementation of computational pipelines to analyze next generation sequencing data, gene expression studies, prediction of macromolecular 3D structures, drug design, precision medicine, phylogenetic studies, amongst many others.
This multitude of applications means that bioinformaticians also tend to have different specialties. It is relatively rare to find a bioinformatician that possesses experience in all or even many of these applications. Life science data is diverse, expansive and complex. Mining such “big data” to extract useful knowledge is complicated and requires careful analysis using appropriate techniques. Mistakenly, bioinformaticians might be seen as “a jack of all trades” by some life scientists, who may think that a bioinformatician should be able to do all types of analysis quickly just by running a few lines of code.
To achieve a successful collaboration, it is crucial that all contributory parties clearly establish the goals, requirements and scope of the project, allowing the right person(s) to be recruited for the right task. For example, if a specific algorithm or computational tool must be developed for a project, it would be more relevant to recruit a bioinformatician with a computer engineering background who can rapidly develop the desired tool. Alternatively, if assistance in data analysis is needed to answer a specific biological question, then it would be better to recruit a bioinformatician with a biological background, who could better comprehend the research context and apply or modify appropriate tools and pipelines to fulfill the needs of the research group. Since biological applied research often involves several rounds of data analyses, data optimization based on feedback, and repetition of pipelines on different datasets, strong lines of communication are essential.
Similar principles should be considered when selecting the leaders/coordinators to manage multidisciplinary projects. A bioinformatics leader should be familiar with the challenges of a broad diversity of bioinformatics applications. He or she should be acutely aware that applied works are as challenging as development tasks and that sufficient time and resources should be allocated to teaching bioinformatics to biologists. It is crucial to understand the needs of life science researchers and to plan resources accordingly so that those needs can be met. The leader of a bioinformatics group should also ensure that the right person(s) is assigned to each project and that whoever requested bioinformatics help is comfortable with the person and process allocated to them.
Assignment of credit
Appropriate assignment of credit is another important factor to maintaining a high level of motivation in collaborations between life science and bioinformatics experts. Credit should be distributed fairly between those who own the scientific idea, those who produce the primary data, and those who add value to it through data analysis or the development of analytical tools. Assigning credit in multidisciplinary projects is a relative concept, and it can be a significant source of conflict, being very much dependent on the characteristics, scope and contributors of a project.
If development of algorithms and computational pipelines is the main focus of the project, most of the credit is attributed to the bioinformaticians whereas, in applied works, partitioning of credit can be more challenging because measuring added value and comparing it among contributors is difficult. Since the life sciences largely remain the domain of biologists, there might be a risk for bioinformaticians to be viewed more of as service providers rather than scientific partners.
Conclusion
Conducting multidisciplinary projects is challenging and success requires a coordinated effort by all contributing disciplines. To facilitate the cooperation necessary between bioinformaticians and life scientists, firstly, it is important to bear in mind that the life sciences and bioinformatics are dependent on each other. Without bioinformatics it would be impossible to manage and analyze the ever-growing amounts of data from life science research and, without that “big data”, bioinformatics could not gain its prestige.
Secondly, human resources have a central role in creating the good working relationships necessary to enable successful collaborations. It is crucial to find a suitable bioinformatician for each role, to be clear about expectations, to provide opportunities for skill development, and to listen to feedback, all of which will help ensure that good bioinformaticians are retained. Managers have a very important role in facilitating collaborations, and it is their responsibility to create an environment that bolsters employee satisfaction because “people leave managers, not companies”.
Thirdly, the needs, interests and benefits for both sides of a collaboration should be well aligned. Only when everything is based on mutual advantage can optimal performance be attained and everyone involved can prosper. To achieve that, it is better if life scientists invite participation from bioinformaticians during the planning phase of their projects.
Finally, measuring the quality of the collaborative relationship is very important. Efforts should be made to find and apply suitable methods to regularly assess such relationships.
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