Molecular Control of Toxin Expression in Snake Venom Gland Organoids

This PhD opportunity is being offered as part of the LSTM and Lancaster University Doctoral Training Partnership. Find out more about the studentships and how to apply

Abstract Snake venom gland organoids (VGOs) represent one of the major advancements in venom research over the last decade and are among the few non-mammalian organoid systems developed to date. These lab-grown mini-organs offer a unique opportunity to study venom production outside of the animal, opening the door to scalable in vitro venom production for research and therapeutic development. Yet, current VGOs still face key challenges: optimising venom yields and replicating the full complexity of toxins found in natural venom. This PhD project will tackle these challenges by uncovering the neuronal regulatory signals that control venom synthesis in snake glands. Like other exocrine organs, snake venom glands respond to neuronal cues that coordinate protein production and secretion—mechanisms that remain largely unexplored in venom systems. By identifying and manipulating these regulatory pathways in VGOs, the project aims to boost venom yields and capture the natural diversity of toxin expression. Beyond advancing organoid technology, this work will help explain why toxin gene expression varies across snake species—variability that complicates antivenom effectiveness and snakebite treatment worldwide. Outcomes of this research will not only provide transformative insights into the molecular control of venom production but also accelerate the translational applications of snake VGOs, from bioprospecting for new drugs to developing more effective antivenoms. This project offers a rare chance to work at the cutting edge of organoid biology, exocrine physiology, and global health.
Where does this project lie in the translational pathway? T1 - Basic Research
Methodological Aspects This PhD will combine experimental and analytical approaches to study how snake venom glands regulate toxin production, which will include:
  • Culture and maintenance of snake venom gland organoids
  • Single-cell and multi-omics data analysis
  • Array Tomography Scanning Electron Microscopy (AT-SEM) – high-resolution 3D imaging
  • Pharmacological receptor studies
  • Biochemistry-based venom activity assays
Expected Outputs Expected outputs include:
  • High-quality publications: At least 2-3 peer-reviewed research papers in internationally recognised journals
  • Conference presentation: Opportunities to present findings at national and international meetings
  • Methodological advancements in the field: Establishment of robust protocols for working with snake venom gland organoids
  • Translational impact: Generating scalable, lab-based venom production for antivenom development or toxin bioprospecting for drug discovery.
Training Opportunities The student will gain expertise in organoid culture, molecular biology, venom biochemistry, bioinformatics, imaging (e.g., AT-SEM), and integrative experimental design—skills with wide applicability in biomedical and biotechnology careers.
Skills Required The ideal candidate will have a strong background in biological sciences, with laboratory experience in molecular biology, cell culture, protein analysis, or pharmacology/neurology. They should be detail-oriented and motivated to work both independently and collaboratively on interdisciplinary areas of the project.
Subject Areas Neglected Tropical Diseases
Key Publications associated with this project

Post Y, Puschhof J, Beumer J, Kerkkamp HM, de Bakker MAG, Slagboom J, de Barbanson B, Wevers NR, Spijkers XM, Olivier T et al: Snake Venom Gland Organoids. Cell 2020, 180(2):233-247.

Puschhof J, Post Y, Beumer J, Kerkkamp HM, Bittenbinder M, Vonk FJ, Casewell NR, Richardson MK, Clevers H: Derivation of snake venom gland organoids for in vitro venom production. Nature Protocols 2021, 16(3):1494-1510.

Modahl CM, Han SX, van Thiel J, Vaz C, Dunstan NL, Frietze S, Jackson TNW, Mackessy SP, Kini RM: Distinct regulatory networks control toxin gene expression in elapid and viperid snakes. BMC Genomics 2024, 25(1):186.

Yamanouye N, Britto LR, Carneiro SM, Markus RP: Control of venom production and secretion by sympathetic outflow in the snake Bothrops jararaca. The Journal of Experimental Biology 1997, 200(19):2547-2556.