Can a biologist fix a smartphone?—Just hack it!

Biological systems integrate multiscale processes and networks and are, therefore, viewed as difficult to dissect. However, because of the clear-cut separation between the software code (the information encoded in the genome sequence) and hardware (organism), genome editors can operate as software engineers to hack biological systems without any particularly deep understanding of the complexity of the systems. This article was inspired by the influential and entertaining essay by Yuri Lazebnik who argued that there are fundamental flaws in how biologists approach problems [1]. Lazebnik proposed that the complexity of biological systems calls for a systems approach to the study of living systems using a radio as a colourful metaphor to illustrate his points [1]. He postulated that, conceptually, a radio functions similarly to a biological system by converting a signal from one form into another using a signal transduction pathway [1]. Here I argue that Lazebnik’s thesis is limited by two fundamental principles of biology. First, the clear-cut separation between the software code—the operating information for living systems as written in the genome sequence—and hardware, or the organism itself [2, 3]. Second, biological systems are not optimally designed but are shaped by historicity—the historical constraints that are integral to their evolution [4]. This limits the extent to which principles of design and engineering can be useful in understanding and manipulating the structures and functions of living organisms. In contrast, modern day biologists are starting to operate as software engineers to hack biological systems and write apps despite a somewhat superficial understanding of the underlying complexity of these systems

People, not papers? A good mentor guides students to publish their work

Read it on Medium (recommended). A nurturing academic mentor prioritizes the growth and development of students, but that shouldn’t come at the expense of publishing. And by publishing, I mean all forms of publications

5 tips on how to navigate the onsite interview for an academic position

Read it on Medium (recommended). Congratulations! You’ve been selected for an in-person interview for a faculty position. Here is 5 tips to help you make a lasting impression during your interview. --- 1. Keep your presentation accessible 2. Don't forget your role as a lecturer and mentor 3. Beyond the CV 4. Address your weaknesses 5. Act and think like a faculty membe

The plant-pathogen haustorial interface at a glance

Many filamentous pathogens invade plant cells through specialized hyphae called haustoria. These infection structures are enveloped by a newly synthesized plant-derived membrane called the extrahaustorial membrane (EHM). This specialized membrane is the ultimate interface between the plant and pathogen, and is key to the success or failure of infection. Strikingly, the EHM is reminiscent of host-derived membrane interfaces that engulf intracellular metazoan parasites. These perimicrobial interfaces are critical sites where pathogens facilitate nutrient uptake and deploy virulence factors to disarm cellular defenses mounted by their hosts. Although the mechanisms underlying the biogenesis and functions of these host-microbe interfaces are poorly understood, recent studies have provided new insights into the cellular and molecular mechanisms involved. In this Cell Science at a Glance and the accompanying poster, we summarize these recent advances with a specific focus on the haustorial interfaces associated with filamentous plant pathogens. We highlight the progress in the field that fundamentally underpin this research topic. Furthermore, we relate our knowledge of plant-filamentous pathogen interfaces to those generated by other plant-associated organisms. Finally, we compare the similarities between host-pathogen interfaces in plants and animals, and emphasize the key questions in this research area

Boosting plant immunity with CRISPR/Cas

CRISPR/Cas has recently been transferred to plants to make them resistant to geminiviruses, a damaging family of DNA viruses. We discuss the potential and the limitations of this method.See related Research: http://www.genomebiology.com/2015/16/1/238

A two disulfide bridge Kazal domain from Phytophthora exhibits stable inhibitory activity against serine proteases of the subtilisin family

BACKGROUND: Kazal-like serine protease inhibitors are defined by a conserved sequence motif. A typical Kazal domain contains six cysteine residues leading to three disulfide bonds with a 1–5/2–4/3–6 pattern. Most Kazal domains described so far belong to this class. However, a novel class of Kazal domains with two disulfide bridges resulting from the absence of the third and sixth cysteines have been found in biologically important molecules, such as human LEKTI, a 15-domain inhibitor associated with the severe congenital disease Netherton syndrome. These domains are referred to as atypical Kazal domains. Previously, EPI1, a Kazal-like protease inhibitor from the oomycete plant pathogen Phytophthora infestans, was shown to be a tight-binding inhibitor of subtilisin A. EPI1 also inhibits and interacts with the pathogenesis-related P69B subtilase of the host plant tomato, suggesting a role in virulence. EPI1 is composed of two Kazal domains, the four-cysteine atypical domain EPI1a and the typical domain EPI1b. RESULTS: In this study, we predicted the inhibition constants of EPI1a and EPI1b to subtilisin A using the additivity-based sequence to reactivity algorithm (Laskowski algorithm). The atypical domain EPI1a, but not the typical domain EPI1b, was predicted to have strong inhibitory activity against subtilisin A. Inhibition assays and coimmunoprecipitation experiments showed that recombinant domain EPI1a exhibited stable inhibitory activity against subilisin A and was solely responsible for inhibition and interaction with tomato P69B subtilase. CONCLUSION: The finding that the two disulfide bridge atypical Kazal domain EPI1a is a stable inhibitor indicates that the missing two cysteines and their corresponding disulfide bond are not essential for inhibitor reactivity and stability. This report also suggests that the Laskowski algorithm originally developed and validated with typical Kazal domains might operate accurately for atypical Kazal domains

How do filamentous pathogens deliver effector proteins into plant cells?

Fungal and oomycete plant parasites are among the most devastating pathogens of food crops. These microbes secrete effector proteins inside plant cells to manipulate host processes and facilitate colonization. How these effectors reach the host cytoplasm remains an unclear and debated area of plant research. In this article, we examine recent conflicting findings that have generated discussion in the field. We also highlight promising approaches based on studies of both parasite and host during infection. Ultimately, this knowledge may inform future broad spectrum strategies for protecting crops from such pathogens

NLR singletons, pairs, and networks:evolution, assembly, and regulation of the intracellular immunoreceptor circuitry of plants

NLRs are modular plant and animal proteins that are intracellular sensors of pathogen-associated molecules. Upon pathogen perception, NLRs trigger a potent broad-spectrum immune reaction known as the hypersensitive response. An emerging paradigm is that plant NLR immune receptors form networks with varying degrees of complexity. NLRs may have evolved from multifunctional singleton receptors, which combine pathogen detection (sensor activity) and immune signalling (helper or executor activity) into a single protein, to functionally specialized interconnected receptor pairs and networks. In this article, we highlight some of the recent advances in plant NLR biology by discussing models of NLR evolution, NLR complex formation, and how NLR (mis)regulation modulates immunity and autoimmunity. Multidisciplinary approaches are required to dissect the evolution, assembly, and regulation of the immune receptor circuitry of plants. With the new conceptual framework provided by the elucidation of the structure and activation mechanism of a plant NLR resistosome, this field is entering an exciting era of research

The Blast Fungus Decoded:Genomes in Flux

Plant disease outbreaks caused by fungi are a chronic threat to global food security. A prime case is blast disease, which is caused by the ascomycete fungus Magnaporthe oryzae (syn. Pyricularia oryzae), which is infamous as the most destructive disease of the staple crop rice. However, despite its Linnaean binomial name, M. oryzae is a multihost pathogen that infects more than 50 species of grasses. A timely study by P. Gladieux and colleagues (mBio 9:e01219-17, 2018, https://doi.org/10.1128/mBio.01219-17) reports the most extensive population genomic analysis of the blast fungus thus far. M. oryzae consists of an assemblage of differentiated lineages that tend to be associated with particular host genera. Nonetheless, there is clear evidence of gene flow between lineages consistent with maintaining M. oryzae as a single species. Here, we discuss these findings with an emphasis on the ecologic and genetic mechanisms underpinning gene flow. This work also bears practical implications for diagnostics, surveillance, and management of blast diseases

How to trick a plant pathogen?

Plants can get sick too. In fact, they get infected by all types of microbes and little critters. But plants have evolved an effective immune system to fight off pathogen invasion. Amazingly, nearly every single plant cell is able to protect itself and its neighbours against infections. The plant immune system gets switched on when one of its many immune receptors matches a ligand in the pathogen. As a consequence of a long evolutionary history of fighting off pathogens, immune receptors are now encoded by hundreds of genes that populate the majority of plant genomes. Understanding how the plant immune system functions and how it has evolved can give invaluable insights that would benefit modern agriculture and help breeding disease-resistant crops