When Do Tumours Develop? Neoplastic Processes Across Different Timescales: Age, Season and Round the Circadian Clock.

While it is recognised that most, if not all, multicellular organisms harbour neoplastic processes within their bodies, the timing of when these undesirable cell proliferations are most likely to occur and progress throughout the organism's lifetime remains only partially documented. Due to the different mechanisms implicated in tumourigenesis, it is highly unlikely that this probability remains constant at all times and stages of life. In this article, we summarise what is known about this variation, considering the roles of age, season and circadian rhythm.

The molecular evolution of cancer associated genes in mammals.

Cancer is a disease that many multicellular organisms have faced for millions of years, and species have evolved various tumour suppression mechanisms to control oncogenesis. Although cancer occurs across the tree of life, cancer related mortality risks vary across mammalian orders, with Carnivorans particularly affected. Evolutionary theory predicts different selection pressures on genes associated with cancer progression and suppression, including oncogenes, tumour suppressor genes and immune genes.

Complex associations between cancer progression and immune gene expression reveals early influence of transmissible cancer on Tasmanian devils.

The world's largest extant carnivorous marsupial, the Tasmanian devil, is challenged by Devil Facial Tumor Disease (DFTD), a fatal, clonally transmitted cancer. In two decades, DFTD has spread across 95% of the species distributional range. A previous study has shown that factors such as season, geographic location, and infection with DFTD can impact the expression of immune genes in Tasmanian devils.

Understanding the evolution of immune genes in jawed vertebrates.

Driven by co-evolution with pathogens, host immunity continuously adapts to optimize defence against pathogens within a given environment. Recent advances in genetics, genomics and transcriptomics have enabled a more detailed investigation into how immunogenetic variation shapes the diversity of immune responses seen across domestic and wild animal species. However, a deeper understanding of the diverse molecular mechanisms that shape immunity within and among species is still needed to gain insight into-and generate evolutionary hypotheses on-the ultimate drivers of immunological differences.

Transmissible cancer and longitudinal telomere dynamics in Tasmanian devils (Sarcophilus harrisii).

A plethora of intrinsic and environmental factors have been shown to influence the length of telomeres, the protector of chromosome ends. Despite the growing interest in infection-telomere interactions, there is very limited knowledge on how transmissible cancers influence telomere maintenance. An emblematic example of transmissible cancer occurs in the Tasmanian devil (Sarcophilus harrisii), whose populations have been dramatically reduced by infectious cancer cells.

Telomeres, the loop tying cancer to organismal life-histories.

Recent developments in telomere and cancer evolutionary ecology demonstrate a very complex relationship between the need of tissue repair and controlling the emergence of abnormally proliferating cells. The trade-off is balanced by natural and sexual selection and mediated via both intrinsic and environmental factors. Here, we explore the effects of telomere-cancer dynamics on life history traits and strategies as well as on the cumulative effects of genetic and environmental factors.

Transmissible cancer influences immune gene expression in an endangered marsupial, the Tasmanian devil (Sarcophilus harrisii).

Understanding the effects of wildlife diseases on populations requires insight into local environmental conditions, host defence mechanisms, host life-history trade-offs, pathogen population dynamics, and their interactions. The survival of Tasmanian devils (Sarcophilus harrisii) is challenged by a novel, fitness limiting pathogen, Tasmanian devil facial tumour disease (DFTD), a clonally transmissible, contagious cancer. In order to understand the devils' capacity to respond to DFTD, it is crucial to gain information on factors influencing the devils' immune system.

Targeted mutagenesis in Nicotiana tabacum ADF gene using shockwave-mediated ribonucleoprotein delivery increases osmotic stress tolerance.

DNA-free genome editing involves the direct introduction of ribonucleoprotein (RNP) complexes into cells, but this strategy has rarely been successful in plants. In the present study, we describe a new technique for the introduction of RNPs into plant cells involving the generation of cavitation bubbles using a pulsed laser. The resulting shockwave achieves the efficient transfection of walled cells in tissue explants by creating transient membrane pores.

Transmissible Cancers in an Evolutionary Perspective.

Inter-individual transmission of cancer cells represents an intriguing and unexplored host-pathogen system, with significant ecological and evolutionary ramifications. The pathogen consists of clonal malignant cell lines that spread horizontally as allografts and/or xenografts. Although only nine transmissible cancer lineages in eight host species from both terrestrial and marine environments have been investigated, they exhibit evolutionary dynamics that may provide novel insights into tumor-host interactions particularly in the formation of metastases.

Fifth International Biannual Evolution and Ecology of Cancer Conference (Cooperation, Conflict and Parasitism) meeting report-Wellcome Genome Campus, Hinxton, UK.

The fifth biannual conference of the International Society of Evolution and Ecology of Cancer (ISEEC) was held between the 17th and 19th of July 2019 in Hinxton (UK) at the Wellcome Genome Campus. The main theme of the conference: cooperation, conflict and parasitism reflected our growing understanding of the role cancer has played in the evolution of multicellular organisms, as well as the urgent need of translating these Darwinian processes to treatment strategies. Below we provide a brief summary of each plenary sessions and other oral presentations, to bring the conference to the broader audience of evolutionary biology and applications.

Dipteran Attraction to a Variety of Baits: Implications for Trapping Studies as a Tool for Establishing Seasonal Presence of Significant Species.

Monitoring and collection of fly taxa (Diptera: Calliphoridae; Muscidae; Sarcophagidae) of medical, veterinary, and agricultural importance is often routine practice, providing data on target species presence, distribution and abundance. Collection practices currently involve baited trapping and while an inherent bias accompanying the choice of bait is acknowledged, there is little consistency in bait choice between studies and insufficient assessment of trapping success rates for bait types in current use. This study aimed to examine the effect of bait choice on trapping results for six commonly used bait types; a commercial bait (Envirosafe Fly Attractant, Envirosafe Products) and a combination of mixtures of liver, horse manure and 5% sodium sulfide (Na2S).

Genetic diversity, inbreeding and cancer.

Genetic diversity is essential for adaptive capacities, providing organisms with the potential of successfully responding to intrinsic and extrinsic challenges. Although a clear reciprocal link between genetic diversity and resistance to parasites and pathogens has been established across taxa, the impact of loss of genetic diversity by inbreeding on the emergence and progression of non-communicable diseases, such as cancer, has been overlooked. Here we provide an overview of such associations and show that low genetic diversity and inbreeding associate with an increased risk of cancer in both humans and animals.

Cancer Is Not (Only) a Senescence Problem.

Age is one of the strongest predictors of cancer and risk of death from cancer. Cancer is therefore generally viewed as a senescence-related malady. However, cancer also exists at subclinical levels in humans and other animals, but its earlier effects on the body are poorly known by comparison.

Evolved Dependence in Response to Cancer.

Evolved dependence is a process through which one species becomes 'dependent' on another following a long evolutionary history of interaction. This happens when adaptations selected in the first species for interacting lead to fitness costs when the second species is not encountered. Evolved dependence is frequent in host-parasite interactions, where hosts may achieve a higher fitness in the presence of the parasite than in its absence.

Oncogenesis as a Selective Force: Adaptive Evolution in the Face of a Transmissible Cancer.

Similar to parasites, malignant cells exploit the host for energy, resources and protection, thereby impairing host health and fitness. Although cancer is widespread in the animal kingdom, its impact on life history traits and strategies have rarely been documented. Devil facial tumour disease (DFTD), a transmissible cancer, afflicting Tasmanian devils (Sarcophilus harrisii), provides an ideal model system to monitor the impact of cancer on host life-history, and to elucidate the evolutionary arms-race between malignant cells and their hosts.

Purifying selection and concerted evolution of RNA-sensing toll-like receptors in migratory waders.

Migratory birds encounter a broad range of pathogens during their journeys, making them ideal models for studying immune gene evolution. Despite the potential value of these species to immunoecology and disease epidemiology, previous studies have typically focused on their adaptive immune gene repertoires. In this study, we examined the evolution of innate immune genes in three long-distance migratory waders (order Charadriiformes).

Plant Cell-Based Recombinant Antibody Manufacturing with a 200 L Orbitally Shaken Disposable Bioreactor.

Tobacco BY-2 cells are an attractive platform for the manufacture of a variety of biopharmaceutical proteins, including antibodies. Here, we describe the scaled-up cultivation of human IgG-secreting BY-2 cells in a 200 L orbitally shaken disposable bioreactor, resulting in cell growth and recombinant protein yields that are proportionately comparable with those obtained from cultivations in 500 mL shake flasks. Furthermore, we present an efficient downstream process for antibody recovery from the viscous spent culture medium using expanded bed adsorption (EBA) chromatography.

High-yield production of a human monoclonal IgG by rhizosecretion in hydroponic tobacco cultures.

Rhizosecretion of recombinant pharmaceuticals from in vitro hydroponic transgenic plant cultures is a simple, low cost, reproducible and controllable production method. Here, we demonstrate the application and adaptation of this manufacturing platform to a human antivitronectin IgG1 monoclonal antibody (mAb) called M12. The rationale for specific growth medium additives was established by phenotypic analysis of root structure and by LC-ESI-MS/MS profiling of the total protein content profile of the hydroponic medium.

In situ cell retention of a CHO culture by a reverse-flow diafiltration membrane bioreactor.

Heterogeneities occur in various bioreactor designs including cell retention devices. Whereas in external devices changing environmental conditions cannot be prevented, cells are retained in their optimal environment in internal devices. Conventional reverse-flow diafiltration utilizes an internal membrane device, but pulsed feeding causes temporal heterogeneities.

Scaled-up manufacturing of recombinant antibodies produced by plant cells in a 200-L orbitally-shaken disposable bioreactor.

Tobacco BY-2 cells have emerged as a promising platform for the manufacture of biopharmaceutical proteins, offering efficient protein secretion, favourable growth characteristics and cultivation in containment under a controlled environment. The cultivation of BY-2 cells in disposable bioreactors is a useful alternative to conventional stainless steel stirred-tank reactors, and orbitally-shaken bioreactors could provide further advantages such as simple bag geometry, scalability and predictable process settings. We carried out a scale-up study, using a 200-L orbitally-shaken bioreactor holding disposable bags, and BY-2 cells producing the human monoclonal antibody M12.

Correlation between mass transfer coefficient kLa and relevant operating parameters in cylindrical disposable shaken bioreactors on a bench-to-pilot scale.

Background: Among disposable bioreactor systems, cylindrical orbitally shaken bioreactors show important advantages. They provide a well-defined hydrodynamic flow combined with excellent mixing and oxygen transfer for mammalian and plant cell cultivations. Since there is no known universal correlation between the volumetric mass transfer coefficient for oxygen kLa and relevant operating parameters in such bioreactor systems, the aim of this current study is to experimentally determine a universal kLa correlation.

Molecular farming in tobacco hairy roots by triggering the secretion of a pharmaceutical antibody.

Recombinant pharmaceutical proteins expressed in hairy root cultures can be secreted into the medium to improve product homogeneity and to facilitate purification, although this may result in significant degradation if the protein is inherently unstable or particularly susceptible to proteases. To address these challenges, we used a design of experiments approach to develop an optimized induction protocol for the cultivation of tobacco hairy roots secreting the full-size monoclonal antibody M12. The antibody yield was enhanced 30-fold by the addition of 14 g/L KNO3 , 19 mg/L 1-naphthaleneacetic acid and 1.

Optimization of BY-2 cell suspension culture medium for the production of a human antibody using a combination of fractional factorial designs and the response surface method.

We have developed a strategy for the optimization of plant cell suspension culture media using a combination of fractional factorial designs (FFDs) and response surface methodology (RSM). This sequential approach was applied to transformed tobacco BY-2 cells secreting a human antibody (M12) into the culture medium, in an effort to maximize yields. We found that the nutrients KNO₃, NH₄NO₃ and CaCl₂ and the hormones 2,4-dichlorophenoxyacetic acid (2,4-D) and 6-benzylaminopurine (BAP) had the most significant impact on antibody accumulation.