Derric David Nimmo

• Manager at Oxitec Ltd

With the recent revolution in molecular biology many desirable traits can now be engineered into in a wide range of organisms. Genetic engineering of plants and animals is becoming a standard and powerful tool to improve and protect crops and prevent diseases. Transgenic plants have driven the regulatory landscape so far, but other organisms are no...

Aedes aegypti is the primary vector of dengue fever, a viral disease which has an estimated incidence of 390 million infections annually. Conventional vector control methods have been unable to curb the transmission of the disease. We have previously reported a novel method of vector control using a tetracycline repressible self-limiting strain of...

BackgroundOX513A is a genetically-engineered strain of Ae. aegypti carrying a repressible, dominant inherited transgene that confers lethality in immature heterozygous progeny. Released male OX513A adults have proven effective for the localised suppression of wild Ae. aegypti, highlighting its potential in vector control. Mating and life table asse...

Traditional mosquito control strategies rely heavily on the use of chemical insecticides. However, concerns about the efficiency of traditional control methods, environmental impact and emerging pesticide resistance have highlighted the necessity for developing innovative tools for mosquito control. Some novel strategies, including release of insec...

New techniques and methods are being sought to try to win the battle against mosquitoes. Recent advances in molecular techniques have led to the development of new and innovative methods of mosquito control based around the Sterile Insect Technique (SIT)1-3. A control method known as RIDL (Release of Insects carrying a Dominant Lethal)4, is based a...

In Drosophila melanogaster the doublesex (dsx) and fruitless (fru) regulatory genes act at the bottom of the somatic sex determination pathway. Both are regulated via alternative splicing by an upstream female-specific TRA/TRA-2 complex, recognizing a common cis element. dsx controls somatic sexual differentiation of non-neural as well as of neural...

Aedes mosquitoes include important vector species such as Aedes aegypti, the major vector of dengue. Genetic control methods are being developed for several of these species, stimulated by an urgent need owing to the poor effectiveness of current methods combined with an increase in chemical pesticide resistance. In this review we discuss the vario...

OX513A is a transgenic strain of Aedes aegypti engineered to carry a dominant, non-sex-specific, late-acting lethal genetic system that is repressed in the presence of tetracycline. It was designed for use in a sterile-insect (SIT) pest control system called RIDL® (Release of Insects carrying a Dominant Lethal gene) by which transgenic males are re...

Dengue is the most important mosquito-borne viral disease. No specific treatment or vaccine is currently available; traditional vector control methods can rarely achieve adequate control. Recently, the RIDL (Release of Insect carrying Dominant Lethality) approach has been developed, based on the sterile insect technique, in which genetically engine...

Summary of results. The table shows the mean and (in brackets) standard deviation for each of the parameters measured, for Tx. spendens and Tx. amboinensis fed on WT (control), OX513A reared off tetracycline (OX513A OFF TET) and OX513A reared on tetracycline (OX513A ON TET). The results for females (F), males (M) and those individuals that did not...

In Drosophila melanogaster the doublesex (dsx) and fruitless (fru) regulatory genes act at the bottom of the somatic sex determination pathway. Both are regulated via alternative splicing by an upstream female-specific TRA/TRA-2 complex, recognizing a common cis element. dsx controls somatic sexual differentiation of non-neural as well as of neural...

Censor analysis of Aeafru introns. Graphical output of Censor analysis on Aeafru intron sequences. For a legend see: http://www.girinst.org/censor/help.html#GRAPH. For the intron 1 (424 kb-long) the output is reported for the whole sequence and for 42,4 kb-long sub regions of the same intron. For each Aeafru intron the number of repetitive elements...

Exon/Intron junctions and MaxEntScan scores of fru genes. A) Coding sequences are shown in upper case letters and non-coding regions in lower case letters. The 5′ss consensus sequence is MAG/GTRAGT and the 3′ss consensus is YnNYAG. The number of pyrimidines (N° of Y) in the 12 bp preceding the 3′ ss (NYAG) is indicated for each 3′ss. The consensus...

Correspondence between MEME identified motifs and motif from RegRNA database. The nucleotides of MEME motifs corresponding to RegRNA motifs areshaded in light grey. (PDF)

Microsyntheny of mosquitoes fru containing regions. Ensembl genome browser view of the fru containing regions of Ae. aegypti and An. gambiae genomes. The homologues are connected by braked lines. The green arrow indicates a putative chromosomal breakpoint site involved in genomic rearrangement after the split of the two species. Only 3 genes (Aeafr...

Consensus sequences of TRA/TRA-2 binding sites. Consensus sequences of TRA/TRA-2 binding sites of D. melanogaster, An. gambiae and Ae. aegypti dsx, fru and dsx+fru genes obtained with WebLogo web tool. The absence of a consensus is clear for mosquitoes genes. (PDF)

Graphical representation and list of motifs identified by MEME analysis. Schematic graphical representation and tabular list of the motifs identified by MEME analysis in Aeafru and Aeadsx genes. (PDF)

Lists of primers, GenBank accession numbers and web tools utilized in this paper. (PDF)

Schematic representation of the position of the identified putative cis-elements involved in splicing regulation of Aeadsx and Aeafru. We identified in Aeafru P1 exon an additional putative TRA/TRA-2 binding site located close to the male-specific 5′ss, which appears to be highly conserved in the very same region of Drosophila fru, although previou...

Modified Censor output of repetitive elements identified in Aeafru intronic regions. The identified repetitive elements greatly vary in length and among them the most abundant are the NON-LTR/Jockey LINE-1_AA element [86], detected in 38 copies, and the NON-LTR/SINE Feilai elements [87], detected in 36 copies. (PDF)

Regulatory elements in the sex-specifically regulated region of fru homologs. Sequence of the putative Aeafru cis identified in the female-specific exon P1-f. The upper case indicate conserved nucleotides respect to the consensus sequences of Drosophila. The distance of these elements from the male- and female-specific 5′ splicing donor sites are i...

Ae. aegypti intron analysis. Tabular output of Aedes aegypti intron analysis. The average number of repetitive elements per kb (indicated as NoRE/kb) in Aeafru introns is 2,03±0,28 while the average percentage of nucleotides of the identified repetitive elements with the respect to the nucleotides of the Aeafru introns (indicated as REbp) is 34,56%...

Dengue is the most important mosquito-borne viral disease. In the absence of specific drugs or vaccines, control focuses on suppressing the principal mosquito vector, Aedes aegypti, yet current methods have not proven adequate to control the disease. New methods are therefore urgently needed, for example genetics-based sterile-male-release methods....

Dengue is the most medically important arthropod-borne viral disease, with 50-100 million cases reported annually worldwide. As no licensed vaccine or dedicated therapy exists for dengue, the most promising strategies to control the disease involve targeting the predominant mosquito vector, Aedes aegypti. However, the current methods to do this are...

The idea of implementing genetics-based insect control strategies modelled on the traditional SIT (Sterile Insect Technique), such as RIDL (Release of Insects carrying a Dominant Lethal), is becoming increasingly popular. In this paper, we compare a genetically modified line of Aedes aegypti carrying a tetracycline repressible, lethal positive feed...

An approach based on mosquitoes carrying a conditional dominant lethal gene (release of insects carrying a dominant lethal, RIDL) is being developed to control the transmission of dengue viruses by vector population suppression. A transgenic strain, designated OX3604C, of the major dengue vector, Aedes aegypti, was engineered to have a repressible...

Genomic DNA sequence analysis of attP integrations. Table shows strain, chromosomal location (chromosome number and arm followed by polytene map division and nucleotide number of insertion) and flanking sequences 5′ and 3′ of the piggyBac insert. All insertion sites are unique and have characteristic TTAA sequence duplications either side of the in...

Oligonucleotides and primers. Oligonucleotides VTET 1 FOR, VTET 1 REV, VTET 2 FOR and VTET 2 REV were annealed to form the Vida3 tetramer insert. Primers 3′FORnew, 3′REVnew, 5′FOR and 5′REV were used for inverse PCR and C5genomicfwd, G5genomicfwd, H5genomicfwd, E5-3R-FWD, pBac PCR rev and 3′REVnew for genomic PCR. Primers attR-F-new, attL-R-new, at...

Mendelian inheritance of fluorescent markers. Hemizygous populations of strains E, G, H and EVida3 were crossed inter-se and egg batches collected from individual females. Approximately 100 F1 progeny, from a minimum of five egg batches for each strain, were screened for fluorescence. All individual F1 populations fitted the expected 3∶1 phenotypic...

Parasite intensity following P. y. nigeriensis infections of strains E and EVida3. Oocysts and melanised ookinetes are scored as invading parasites in all experiments. Boxplots, of data from Figure 4 on the same axes, show parasite intensity for strains E (white boxes) and EVida3 (Grey boxes). Vertical lines denote the 95% confidence interval, hori...

Diseases transmitted by mosquitoes have a devastating impact on global health and this is worsening due to difficulties with existing control measures and climate change. Genetically modified mosquitoes that are refractory to disease transmission are seen as having great potential in the delivery of novel control strategies. Historically the geneti...

Behavioral responses of Aedes aegypti male populations developed for Release of Insects Carrying a Dominant Lethal (RIDL) technology and a Malaysian wild-type population of two age groups (4-5 and 8-10 d old) were tested under laboratory conditions against chemical irritants and repellents using the high-throughput screening system device. Results...

Mendelian inheritance of the transgene in OX3860 lines. (0.03 MB DOC)

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Full flanking sequences of interation sites of OX3860 into Aedes albopictus. (0.03 MB DOC)

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The Asian tiger mosquito, Aedes albopictus (Skuse), is a vector of several arboviruses including dengue and chikungunya. This highly invasive species originating from Southeast Asia has travelled the world in the last 30 years and is now established in Europe, North and South America, Africa, the Middle East and the Caribbean. In the absence of vac...

Dengue and dengue hemorrhagic fever are increasing public health problems with an estimated 50-100 million new infections each year. Aedes aegypti is the major vector of dengue viruses in its range and control of this mosquito would reduce significantly human morbidity and mortality. Present mosquito control methods are not sufficiently effective a...

Two strains of Aedes aegypti, a RIDL ® strain (MyRIDL513A) and a laboratory strain (MyWT), were used in the insecticide-susceptibility study. Two-to-five-day-old female mosquitoes from both strains were tested for their susceptibility against seven insecticides from the class of organophosphate, carbamate, pyrethroids and organochlorine. The adult...

The Sterile Insect Technique (SIT) uses the mass release of sterile insects as a highly effective area-wide, environmentally safe method of pest control. Various uses of genetics to enhance the sterile insect technique for mosquitoes have been proposed since the early 1950's. Using induced mutations, chromosomal rearrangements, breeding and selecti...

Suppression or elimination of vector populations is a tried and tested method for reducing vector-borne disease, and a key component of integrated control programs. Genetic methods have the potential to provide new and improved methods for vector control. The required genetic technology is simpler than that required for strategies based on populati...

Metacestodes of Hymenolepis diminuta secrete a molecule that decreases vitellogenin (Vg) synthesis in the beetle host, Tenebrio molitor. The 5608 bp T. molitor Vg cDNA represents a single-copy gene encoding a single open reading frame of 1821 amino acids with a predicted molecular mass of 206 kDa. Northern blot analysis revealed detectable levels o...

Current techniques for the genetic engineering of insect genomes utilize transposable genetic elements, which are inefficient, have limited carrying capacity and give rise to position effects and insertional mutagenesis. As an alternative, we investigated two site-specific integration mechanisms in the yellow fever mosquito, Aedes aegypti. One was...

ABStrAct: The Sterile Insect Technique (SIT) has been used very successfully against range of pest insects, including various tephritid fruit flies, several moths and a small number of livestock pests. However, modern genetics could potentially provide several improvements that would increase the cost-effectiveness of SIT, and extend the range of s...

On Jun 17, 2005 this sequence version replaced gi:51979159.

The presence of immune molecules induced by microorganisms in the haemolymph of Lutzomyia longipalpis sandflies has been investigated. Injections of Escherichia coli and Micrococcus luteus into female sandflies induced anti-bacterial activity in the haemolymph. Inhibition zone assays showed that haemolymph from E. coli and M.luteus injected sandfli...

Thesis (Ph. D.)--University of Keele, 2000.