Weaving a web of knowledge about silk and venom

To create new materials that mimic the strength and flexibility of black widow spider silk and drugs based on its potent venom, we need a full list of the proteins involved and what they do. Two BMC Genomics papers published today make a start on this task. In this guest post, Jessica Garb, an author on both papers, talks about how she and the team took an inventory of the proteins in black widow spider silk and venom glands, and what this means for biomaterials and medicine.

Photo credit: Marshal Hedin
Photo credit: Marshal Hedin

Spiders are widely admired for two of their most fascinating adaptations: silk and venom production. The silks and venom of black widows (Latrodectus hesperus)  are highly prized because of their impressive properties, which have direct engineering and biomedical applications.

Spider silks are among the toughest known materials, surpassing steel and Kevlar in energy absorption, and black widow silk is particularly notable for its high tensile strength.

Black widow venom is notorious because of its extreme potency on vertebrates, including humans, but it is also an essential tool for studying neuronal signaling. Both silk and venom are protein-rich secretions, making the discovery of genes contributing to their properties particularly amenable to genomic approaches.

Collaboration paves the way

Our team of scientists – from Washington and Lee University, University of Massachusetts Lowell, University of California Riverside, and Harvard Medical School – worked on these studies over several years, culminating in the two BMC Genomics papers that are expected to fuel new research avenues into the genomics of silk and venom for years to come.

Previous studies of silk and venom genes largely focused on a few well-known protein families, but using next-generation sequencing approaches, our two sister papers co-published in BMC GenomicsClarke et al. and Haney et al.) uncover a much wider range of new proteins specifically produced in silk and venom glands.

These findings not only comprehensively inventory the protein constituents of black widow silks and venom, but also reveal additional proteins likely to play an important role in their production. On behalf of all co-authors, I am excited to share these papers’ key results and implications for understanding silk and venom production, its evolution, and their applied potential.

Black widow silk functional genomics

Black widows synthesize six distinct silk fibers and a sticky glue. The fibers and glue are assembled from proteins expressed in specialized abdominal glands, and in black widows there are seven silk types, each one corresponding to one of the six fibers and glue. Every black widow silk type is composed of different proteins, which underlie their distinct mechanical properties, and relates to their function (e.g., one fiber is only used in egg cases, others are used in webs, another for prey wrapping, and the glue is used to trap prey).

Clarke et al. used Illumina sequencing of three tissue types (silk, venom and cephalothorax) from the Western black widow spider to create a catalog of all gene transcripts– the intermediates between genes and proteins. This is a targeted method to inventory all functionally important genes as there isn’t yet a complete genome sequence for this species.

The Illumina instrument produced millions of short sequences, and we used bioinformatics to assemble these pieces into ~100,000 unique transcripts. By comparing the number of short sequences from silk glands to the other two tissues that matched the assembled transcripts, we identified 647 transcripts that are largely expressed in silk glands. Not only did this efficiently recover all the known components of black widow silks, it also revealed a great diversity of glue proteins and unknown proteins that we think might control silk genes.

Black widow venom functional genomics

The extreme potency of black widow venom had been attributed to a single protein (alpha-latrotoxin) known to form calcium channels in vertebrate nerve cells, causing massive neurotransmitter release. Proteins in the same family as alpha-latrotoxin (latrotoxins) are distinctly different in their architecture and function to other venom toxins, and their evolution is mysterious, as only a few sequences were known.

Haney et al. used the black widow gene transcript catalog produced by Clarke et al. to identify 695 transcripts with biased expression in venom glands. This revealed at least 20 distinct latrotoxins, and several other proteins unknown from black widow venom, which may contribute to the severe effects of black widow bites.

The ~100,000 transcript catalog was also used to identify proteins from collected black widow venom using mass spectrometry, which confirmed the presence of many predicted toxins. The results both illuminate and deepen the latrotoxin mystery – this protein family is far more diverse than we imagined, but its origin and distribution are still unclear.

Novel silk and glue transcripts reported in Clarke et al. provide the recipe for recombinant biomaterials, such as super-tough but lightweight textiles and medical devices, or superior adhesives.  The new venom proteins in Haney et al. can be mined for innovative drug leads, molecular tools for neuroscience, and designs to improve antivenoms. This work was made possible by funding from the US National Science Foundation and the National Institutes of Health.

Co-author Websites:

Nadia Ayoub Washington and Lee University

Cheryl Hayashi

Alexander Lancaster, Harvard Medical School

Jessica Garb, University of Massachusetts Lowell

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