Target identification strategies in plant chemical biology

The current needs to understand gene function in plant biology increasingly require more dynamic and conditional approaches opposed to classic genetic strategies. Gene redundancy and lethality can substantially complicate research, which might be solved by applying a chemical genetics approach. Now understood as the study of small molecules and their effect on biological systems with subsequent target identification, chemical genetics is a fast developing field with a strong history in pharmaceutical research and drug discovery. In plant biology however, chemical genetics is still largely in the starting blocks, with most studies relying on forward genetics and phenotypic analysis for target identification, whereas studies including direct target identification are limited. Here, we provide an overview of recent advances in chemical genetics in plant biology with a focus on target identification. Furthermore, we discuss different strategies for direct target identification and the possibilities and challenges for plant biology

Efficient Forward Simulation of Fisher-Wright Populations with Stochastic Population Size and Neutral Single Step Mutations in Haplotypes

In both population genetics and forensic genetics it is important to know how haplotypes are distributed in a population. Simulation of population dynamics helps facilitating research on the distribution of haplotypes. In forensic genetics, the haplotypes can for example consist of lineage markers such as short tandem repeat loci on the Y chromosome (Y-STR). A dominating model for describing population dynamics is the simple, yet powerful, Fisher-Wright model. We describe an efficient algorithm for exact forward simulation of exact Fisher-Wright populations (and not approximative such as the coalescent model). The efficiency comes from convenient data structures by changing the traditional view from individuals to haplotypes. The algorithm is implemented in the open-source R package 'fwsim' and is able to simulate very large populations. We focus on a haploid model and assume stochastic population size with flexible growth specification, no selection, a neutral single step mutation process, and self-reproducing individuals. These assumptions make the algorithm ideal for studying lineage markers such as Y-STR.Comment: 17 pages, 6 figure

Recombination semigroups on measure spaces

The dynamics of recombination in genetics leads to an interesting nonlinear differential equation, which has a natural generalization to a measure valued version. The latter can be solved explicitly under rather general circumstances. It admits a closed formula for the semigroup of nonlinear positive operators that emerges from the forward flow and is, in general, embedded in a multi-parameter semigroup.Comment: 15 page

Non-HLA gene polymorphism in pulmonary tuberculosis

BCG vaccination has been shown to give protection against tuberculosis. However, South Indian (Chingleput) Trial of BCG vaccination did not give any protection against bacillary forms of tuberculosis. A number of hypotheses and possibilities were put forward for this failure (1). One of the possibilities suggested was the genetics of the people (Host genetics) living in that region. Pulmonary tuberculosis is a granulomatous lung disease caused by Mycobactrium tuberculosis. Susceptibility to tuberculosis has been suggested to be multifactorial. Though environmental and socio-economic factors are primarily related, numerous studies have emphasised the importance of host resistance and hereditary susceptibility (2,3)

The Rosetteless gene controls development in the choanoflagellate S. rosetta.

The origin of animal multicellularity may be reconstructed by comparing animals with one of their closest living relatives, the choanoflagellate Salpingoeca rosetta. Just as animals develop from a single cell-the zygote-multicellular rosettes of S. rosetta develop from a founding cell. To investigate rosette development, we established forward genetics in S. rosetta. We find that the rosette defect of one mutant, named Rosetteless, maps to a predicted C-type lectin, a class of signaling and adhesion genes required for the development and innate immunity in animals. Rosetteless protein is essential for rosette development and forms an extracellular layer that coats and connects the basal poles of each cell in rosettes. This study provides the first link between genotype and phenotype in choanoflagellates and raises the possibility that a protein with C-type lectin-like domains regulated development in the last common ancestor of choanoflagellates and animals