Although there are guides to train potential peer reviewers for reviewing research articles, the format and purposes of reviews aren’t the same, so they must be approached from a different perspective and assessed by different criteria. You might even be an established group leader by the first time you’ve been invited to evaluate a review simply because there are just fewer of them than research articles. So, what does an editor expect from your report? Broadly speaking, you can think about it in terms of A, B, Cs.
Accurate
The most important role of a peer reviewer is to make sure that the review articles are scientifically accurate. By this, I mean that statements should be factually correct, with appropriate references that support the conclusions. Accuracy also extends to the structure of the article. For example, does the title and abstract actually reflect what is covered in the review? Figures, although schematic and simplified, should also present the latest interpretation of the data accurately.
Balanced
Next, think about whether the review is balanced. As a whole, think about whether the articles covers everything you’d expect to see on the topic; make sure to point out if a large body of work is missing and check that the reference list isn’t biased! Even for opinion pieces, it is important that review-type articles are balanced and provide both sides of an argument. It is helpful for the authors to point out ongoing debate or controversy in the field, especially for non-specialists who might not be aware of the types of discussions that are happening. Where the authors propose new ideas and hypotheses, it is important that they distinguish these points from established facts. In addition, remember that studies have both strengths and weaknesses, and that techniques or approaches have their advantages and limitations – are both sides acknowledged?
Clear
Review-type articles are read by specialist and non-specialists alike, so it’s important that they are clear and accessible to a broad audience. For journals that developmentally edit or copy edit manuscripts, many of these points will be addressed by the in-house editor – although it is still useful for them to know what you think needs work, even if you don’t provide a point-by-point list of necessary changes.
It’s crucial that language and phrasing is clear and unambiguous to avoid confusion or misinterpretation. As an expert in your field, it might be easy to gloss over an acronym that you’re familiar with or to know that a gene or cell exists by two (or more) names. Take care to check that authors always introduce and define new terms, and use them consistently. Think about whether the structure of the article prepares you for what to expect and whether you can navigate the article easily. Most reviews should guide the reader through the article and provide all the necessary background to make links in thought between data and conclusions. Finally, are the figures well designed, well presented and intuitive? Would additional figures, boxes or tables help to clarify text and illustrate important key points?
Specifics
On occasion, an editor might raise specific queries with you about the manuscript. For example, if the article is very long, they might ask if you can identify specific parts that could be cut. Alternatively, they might notice a lack of recent references and might ask if the article is timely, as well as a whole range of other questions.
Some lastthoughts
Remember to be polite, courteous and constructive in writing your report.
Try to be specific – refer to line or page numbers if you have concerns with a particular statement.
Most articles will be proofread before publication, so there often isn’t the need to list every typo you find.
Do highlight if you think spelling, grammar or punctuation should be addressed, but avoid suggesting that it should be read by a ‘native English speaker’. This suggests that authors with English as a second language write less well then native English speakers – this is simply not the case!
The Department of Genetics and Development invites applications for one tenure-track faculty position at the Assistant Professor level. We are seeking outstanding applicants who use genetic approaches to study developmental or physiological processes. Our department spans a broad range of interests including developmental biology, physiology, DNA repair and recombination, cancer and human genetics. Applicants must hold a Ph.D. and or an M.D. degree and will be expected to develop an internationally recognized extramural funded research program. Interested applicants should submit a curriculum vitae and a statement of research interests, and arrange for three referees to submit letters of recommendation. Columbia University is an Equal Opportunity Employer and the school has allocated resources to target the recruitment of underrepresented minorities and a particular attention will be given to URM applicants.
A postdoctoral position is immediately available for highly motivated recent PhD or MD/PhD graduates in the Singh Lab (https://medicine.vumc.org/person/bhuminder-singh-phd) at the Division of Gastroenterology, Hepatology, and Nutrition at Vanderbilt University Medical Center to participate in basic studies controlling epithelial polarity as well as more translational efforts to develop innovative therapeutic approaches for colorectal cancer (CRC).
Available projects include:
• Regulation of EGFR signaling by polarized trafficking of its ligand epiregulin (EREG) and mechanisms underlying transformation upon apical mistrafficking of EREG;
• Role of receptor tyrosine kinases MET and RON in resistance to EGFR-targeted therapeutics in CRC.
The projects will involve 3D cultures of genetically or pharmacologically manipulated cell lines and CRC organoids and in vivo cancer xenografts. The effects of specific stimuli and contribution of individual molecules will be monitored by live or fixed (confocal) microscopy, cellular signaling, phenotypic assays, multiplex fluorescence imaging, and comparative RNA-seq (single-cell or bulk) or proteomic analysis. Please see recent publications at: https://scholar.google.com/citations?user=Z9Wjl6AAAAAJ&hl=en
Candidates are sought with experience in signal transduction, biochemistry, cell biology, or cancer biology. Individuals are expected to have excellent oral and written communication skills, as well as a track record of productivity.
Please send a CV, a cover letter, and names of three references to Dr. Bhuminder Singh:bhuminder.singh@vumc.org. The position is available immediately.
The research group of Dr Max Yun, ‘Regeneration of Complex Structures in Adult Vertebrates’ at DFG/CRTD Center for Regenerative Therapies Dresden (Germany) & MPI-CBG is searching for a PhD candidate.
The major focus of the group is to understand the molecular and cellular mechanisms underlying regeneration in adult vertebrates, using salamanders (newts and axolotls) as model systems. The group uses a broad range of molecular, genetic, biochemical and advanced imaging techniques to investigate regenerative processes (https://www.crt-dresden.de/de/forschung/research-groups/core-groups/crtd-core-groups/yun/). The group is co-affiliated to the Max Planck Institute of Molecular Cell Biology and Genetics (https://www.mpi-cbg.de/home/).
The project will involve the investigation of regenerative processes in hematopoietic organs so a background in immunology would be an advantage.
Requirements:
-University degree in the areas of Biology/Biochemistry
-Excellent degree marks (top 10% of year)
-Strong motivation to pursue an academic career.
-Strong interest in the group’s field of work
-Experience in experimental laboratory work (Experience in transgenesis and/or amphibian research would be an asset)
-Excellent knowledge of English (written & oral)
-Strong background in experimental design
-Capacity for working independently
-Will to work in an international team within a highly collaborative environment
Interested candidates should send a CV, list of publications, qualifications/research work description and two references/contacts for reference to Dr Maximina Yun (maximina.yun@tu-dresden.de).
In this episode, sponsored by Thermo Fisher Scientific, we’re taking a look at how genomic technologies are transforming cancer care – now and in the future, and the importance of making sure that these advances are available to all.
We look at what the future looks like for both adult and childhood cancers, as well as exploring how important fast genetic testing is to patients and how new technology could help.
With guests:
Greg Simon, past president of the Biden Cancer Initiative and former executive director of the White House Cancer Moonshot Task Force.
Jim Downing – president and CEO of St Jude Children’s Research Hospital
Dr Marianne Grantham, Head of Cytogenetics and Molecular Haematology department at the Royal London Hospital
Kim Wood, Thermo Fisher Scientific’s Clinical Sequencing Division
Research position investigating the mechanisms underlying cardiac morphogenesis
The Bloomekatz laboratory in the Department of Biology at the University of Mississippi in Oxford, MS is seeking a researcher to assist in our investigations of cardiac morphogenesis and disease using zebrafish. Please see our website https://thebloomekatzlaboratory.org for details on our research. The successful candidate will have the opportunity to be involved in all aspects of the research and publication process, from conducting developmental biology experiments and zebrafish husbandry, to analyzing imaging data to writing and publication.
-Interested in joining our dynamic group apply online: https://careers.olemiss.edu, search zebrafish. Salary dependent on experience. This position is eligible for benefits. Anticipated start date Jan 2020.
-Further questions can be directed to Dr. Bloomekatz at josh@olemiss.edu. The University of Mississippi is an EOE/AA/Minorities/Females/ Vet/Disability/Sexual Orientation/Gender Identity/Title VI/Title VII/Title IX/ADA/ADEA employer.
Department of Biological Sciences, College of Sciences and Mathematics
Auburn University
The Department of Biological Sciences at Auburn University invites applications for a tenure-track faculty position beginning Fall 2021 at the rank of Assistant or Associate Professor in Plant Developmental Biology.
We seek a highly collaborative candidate who will examine fundamental mechanisms governing developmental processes in plants. A successful candidate is expected to establish an extramurally funded, internationally recognized research program focused on plant developmental biology. Instructional responsibilities include development of graduate and/or undergraduate courses in plant developmental biology related to their area of emphasis. Faculty will join existing Plant Biologists as well as recent Developmental hires in Marine and Terrestrial systems as an emerging group of Developmental Biologists in the department.
Review of applications will begin December 1, 2020 and will continue until a suitable individual is hired. Applicants should submit curriculum vitae, a description of research interests, a statement of teaching philosophy and experience, and contact information of three professional references. Applicants should endeavor to describe how your past and/or potential contributions in teaching, research, and/or service will serve to advance the College of Sciences and Mathematics’s mission of creating an inclusive environment. This should include the following: Statements of values as they relate to your understanding and commitment to diversity, inclusion, and equity in STEM fields; examples of experiences that demonstrate your commitment to fostering the success of traditionally underrepresented groups in STEM (students, staff, and/or peers) and supporting a diversity of perspectives in the classroom, lab, campus, and/or community; and Future plans for continuing to advance inclusive excellence, diversity, or equity in your research, teaching, and service.
Apply your developmental biology / neurobiology skills to the problem of brain cancer.
The lab of Dr. Jennifer Chan is seeking to recruit a motivated postdoctoral fellow to investigate cell fate decisions during the process of brain tumour development and progression. Research activities in the lab focus on growth factor signalling and transcriptional regulation as determinants of neural precursor identity and fate. We use model systems that include patient-derived glioma cultures, xenografts, and engineered mouse models generated from in utero and post-natal electroporation to address our research questions.
The successful candidate will collaborate with investigators in bioinformatics to apply to apply tools of genomics, epigenomics, and transcriptomics to further define important alterations during neoplastic transformation, including interactions of tumour cells with other constituents in the microenvironment. Early career-stage candidates (within 3 years of receiving PhD or equivalent) with experience in advanced immunohistochemistry / fluorescence microscopy; gene editing, and molecular biology; mouse modeling of disease; and/or experience in genomic approaches like RNA-seq, ChIP-seq, ATAC-seq will be preferentially considered.
The position is available immediately.
Other information
Located in Calgary, Alberta, Canada, the Chan Lab is part of the Charbonneau Cancer Institute at the University of Calgary’s Cumming School of Medicine. Within the Charbonneau Institute, we are part vibrant multidisciplinary research groups focused on childhood cancers and brain cancers. Calgary is a very ‘livable’ and family-friendly city located less than an hour’s drive from the Canadian Rocky Mountains – a haven for outdoor enthusiasts.
Application details:
Submit a brief letter of interest, your academic CV, and the names and contact information of at least three references.
Applications should be submitted as a single PDF file and sent as an email with the subject line “Post-Doctoral Fellowship, Glioma Biology” to: jawchan@ucalgary.ca
Royal Society Publishing has recently published a special issue from Philosophical Transactions B – Contemporary morphogenesis, organized and edited by Kyra Campbell, Emily S Noël, Alexander G Fletcher and Natalia A Bulgakova.
Our brain is immersed in a clear, colourless, nutrient-rich fluid called the cerebrospinal fluid (CSF), which provides mechanical support to the brain and helps to circulate important molecules for brain development and function. Within the interconnected cavities of our brain, the CSF flows in and out constantly. The CSF is actively produced by the choroid plexus (ChP), a highly secretory tissue present at different locations inside the brain cavities.
The ChP-CSF system plays a number of central roles in our brain, such as actively secreting and transporting hormones and nutrients to different brain regions and maintaining the physiological balance of ions and salts. In addition, the ChP is implicated in circadian cycle regulation, influencing the master clock regulation in the brain, and during sleep, CSF flow has been proposed to remove toxic protein aggregates and waste from the brain. Another key function of the ChP is the formation of a selectively permeable barrier, the blood-CSF-barrier, which separates the CSF from the blood, protecting the brain from toxic substances and certain drugs, similar to the blood-brain-barrier.
Despite all these important functions, the ChP and the CSF have long been ignored or dismissed simply as a waste disposal system of the brain, therefore for a long time little was known about these fascinating components of our brain. We now understand a lot more of the development and function of this tissue thanks to research on animal models such as mice, however, the study of human ChP and CSF is still complicated by technical and ethical challenges to obtain biopsies of ChP, particularly at early developmental stages. Studying human CSF is also particularly challenging due to the fact that extraction of this fluid requires painful lumbar punctures which run the risk of blood contamination.
In Madeline Lancaster’s lab at the MRC-LMB in Cambridge, we routinely generate cerebral organoids from human pluripotent stem cells. Cerebral organoids develop neural tissue which expands and matures forming structures that resemble early developmental stages of our brain’s dorsal cortex. Organoids are placed in a supporting media that contains only the essential nutrients and key ingredients that help and sustain brain development. This essential media allows for the spontaneous development of the brain tissue as it would normally develop in vivo, so sometimes we observe the generation of other brain identities other than the desired cerebral cortex. It was in this way that we initially observed the presence of ChP-like tissue adjacent to part of the cerebral cortex. It was this initial observation that prompted us to reproducibly generate ChP tissue. In our recent study entitled “Human CNS barrier-forming organoids with cerebrospinal fluid production” (Pellegrini et al., 2020), we developed a new in vitro model to study early development of human ChP in a dish.
Confocal image of a convoluted ChP organoid sectioned and stained for specific tissue markers
We started using patterning molecules secreted in vivo and previously shown to model ChP development in vitro (Sakaguchi et al., 2015; Watanabe et al., 2012). By adding these molecules at certain timepoint and for a certain duration, the organoids became entirely enriched in ChP tissue. To our surprise we noticed that these organoids would develop various-shaped, clear looking cysts that appeared completely isolated from the pink media surrounding the organoid. Initially, because of the unknown identity of these mysterious cysts, many of these organoids were discarded or considered “failed organoids”. One day, instead of throwing these organoids away we decided to look more carefully at them. By sectioning and staining the tissue with specific markers we came to understand that indeed the cyst was entirely surrounded by ChP.
The first question we had was: are these fluid compartments filled with human CSF? We were able to extract several millilitres of this clear fluid from different organoids. We then decided to perform mass spectrometry analysis to investigate the overall protein composition of the fluid. Together with the fluid extracted from organoids, we also analysed the media as a “negative control” and human in vivo CSF from healthy donors as a “positive control”. The results were quite surprising. The first observation was that this intriguing organoid fluid was not a mere ultrafiltrate of the surrounding media, but a fluid that contained proteins secreted de novo by the ChP. Second, looking at the proteins secreted de novo by the organoid we could find several human CSF proteins, including specific signalling molecules secreted during development, such as Insulin Growth Factor 2 (IGF2), and disease-relevant biomarker such as Serpin Family F Member 1 (SERPINF1) and clusterin (CLU) were indeed present in the organoid fluid, but not in the media. Comparing CSF extracted from organoids at different stages, we could notice a difference in the protein composition, with an enrichment in extracellular matrix proteins at early stages, compared to later stages in which we detected several apolipoproteins involved in lipid metabolism. When we compared our dataset with published proteomic databases of CSF in vivo, we realised that these differences in CSF composition reflected what is reported in embryonic CSF compared to older post-natal CSF stages, matching different stages of maturation.
Another interesting observation is that our organoid-generated CSF lacked blood proteins, such as haemoglobin, which were instead detected in CSF from humans. This is because organoids lack vasculature. We suspect that the presence of these proteins in human CSF is due to contamination from the lumbar punctures used to extract the fluid. Lacking these potential contaminants, the organoid-CSF represents a “cleaner” version of the ChP secretome. These results meant that we were able to generate a close to authentic CSF in a dish, from human cells. Compared to the small amount of CSF one can obtain from mouse embryos, we could extract several millilitres and we could look at the composition of this fluid without any other contaminants.
As mentioned above the ChP forms the blood-CSF-barrier, which regulates the exchange of nutrients and signals from the blood to the CSF, blocking entry of different compounds such as therapeutics. This brain barrier is less studied than the blood-brain-barrier, but it could provide an alternative way to access the brain if appropriately targeted. We therefore wondered: does the ChP in these organoids form a selectively permeable barrier?
Initially, we had a hint that the answer was yes because the liquid inside these cysts is clear, meaning that even the small molecule of phenol red, usually present in our media, is not able to freely cross the barrier. Since we could extract significant amount of fluid from these organoids, the first experiment was simply to add fluorescently labelled molecules of different sizes to the media and observe, after 2 hours of incubation, whether we could detect any fluorescence in the inside of the fluid-filled organoid compartment. Even the smallest of these molecules tested was undetectable inside of the organoid, indicating that the ChP in vitro was indeed forming a barrier. We then wanted to know whether the ChP forming the barrier could select certain molecules instead of others.
While having a coffee with brilliant chemist and friend Dr. Claudia Bonfio, who also works at the MRC-LMB in the completely unrelated field of prebiotic chemistry, we discussed possible ways to detect small molecules in their native state, in a system like the ChP organoids. This unusual meeting between chemistry and biology resulted in the idea of using Nuclear Magnetic Resonance (NMR). Using this technique, we were able to demonstrate the selective permeability of the ChP barrier by challenging the system with two highly similar small molecules with opposite permeabilities such as L-dopa and dopamine. We indeed observed that only L-dopa, and not dopamine, was able to cross the ChP barrier, exactly recapitulating the selectivity observed in vivo. This initial proof of principle experiment was fundamental for us to trust the system and then challenge it with other drugs.
With this experimental approach we were able to show that organoids can qualitatively but also quantitatively predict the permeability of new drugs. When we tested the new drug Sephin 1, a compound that prevents protein misfolding that has recently entered clinical trials, we noticed that the permeability data were slightly lower in the organoids compared to the available data in animals, in this case mice. This indicates that the system could recapitulate permeability of drugs in human, but the levels of transporters expressed in the ChP can be different in other species, reflecting differences in permeability. Finally, we decided to use our method to reveal why the drug BIA 10-2474, which failed clinical trials for multiple conditions including chronic pain and multiple sclerosis, was toxic only in humans. We indeed observed an unusual accumulation of this compound inside the organoid fluid. This observation was consistent with the hypothesis of an accumulation in the CSF of these patients. Together with other toxic effects reported for this drug, the use of ChP organoids could have perhaps have raised some flags during preclinical testing. We think that ChP organoids potentially represent a preclinical in vitro human model to validate safe entry of therapeutics to the brain, with the potential to reduce the number of drugs that fail during clinical trials.
Finally, we were curious to explore in more detail the cellular architecture of the choroid plexus in order to better characterise the different cell populations present in the system. We took advantage of this isolated nature of ChP organoids, not attached to other tissues, to identify cell populations unique to this region of the brain. We looked closely at the ChP and by merging our single cell and proteomic data we were able to learn which specific cell types secrete the biomarkers detected in the organoid CSF fluid. In addition, we identified these obscure “dark” and “light” cells that were first reported in electron micrographs from the ‘70s, but we were also able to discover a new cell type, previously unidentified in the ChP: the myoepithelial cells. These cells have been reported in other secretory tissues such as salivary and mammary glands, and they are enriched in contractile fibres which could potentially help to “squeeze” the secretory epithelial cells to help CSF production.
Artwork by L. Pellegrini representing a section of a brain organoid with both cortical and ChP tissue.
In summary, we learnt that ChP organoids could secrete CSF and form a selectively permeable barrier that can be used to select drugs in a human-specific system in vitro. We also learnt that if you notice something unusual in your experiments, don’t just throw it away!
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In this episode, sponsored by Thermo Fisher Scientific, we’re taking a look at how genomic technologies are transforming cancer care – now and in the future, and the importance of making sure that these advances are available to all.
