![Ti plasmid](https://upload.wikimedia.org/wikipedia/commons/d/d1/Ti_plasmid.svg)
A tumour inducing (Ti)
plasmid
A plasmid is a small, extrachromosomal DNA molecule within a cell that is physically separated from chromosomal DNA and can replicate independently. They are most commonly found as small circular, double-stranded DNA molecules in bacteria; how ...
is a plasmid found in pathogenic species of ''
Agrobacterium
''Agrobacterium'' is a genus of Gram-negative bacteria established by H. J. Conn that uses horizontal gene transfer to cause tumors in plants. '' Agrobacterium tumefaciens'' is the most commonly studied species in this genus. ''Agrobacterium'' i ...
'', including
''A. tumefaciens,
''A. rhizogenes'', ''A. rubi'' and
''A. vitis''.
Evolutionarily, the Ti plasmid is part of a family of plasmids carried by many species of
Alphaproteobacteria
Alphaproteobacteria is a class of bacteria in the phylum Pseudomonadota (formerly Proteobacteria). The Magnetococcales and Mariprofundales are considered basal or sister to the Alphaproteobacteria. The Alphaproteobacteria are highly diverse and ...
. Members of this plasmid family are defined by the presence of a conserved DNA region known as the ''repABC'' gene cassette, which mediates the
replication of the plasmid, the partitioning of the plasmid into daughter cells during
cell division
Cell division is the process by which a parent cell (biology), cell divides into two daughter cells. Cell division usually occurs as part of a larger cell cycle in which the cell grows and replicates its chromosome(s) before dividing. In eukar ...
as well as the maintenance of the plasmid at low copy numbers in a cell.
The Ti plasmids themselves are sorted into different categories based on the type of molecule, or
opine, they allow the bacteria to break down as an energy source.
The presence of this Ti plasmid is essential for the bacteria to cause crown gall disease in plants.
This is facilitated via certain crucial regions in the Ti plasmid, including the ''vir'' region, which encodes for virulence genes, and the
transfer DNA
The transfer DNA (abbreviated T-DNA) is the transferred DNA of the tumor-inducing (Ti) plasmid of some species of bacteria such as ''Agrobacterium tumefaciens'' and ''Agrobacterium rhizogenes(actually an Ri plasmid)''. The T-DNA is transferred fr ...
(T-DNA) region, which is a section of the Ti plasmid that is
transferred via
conjugation
Conjugation or conjugate may refer to:
Linguistics
* Grammatical conjugation, the modification of a verb from its basic form
* Emotive conjugation or Russell's conjugation, the use of loaded language
Mathematics
* Complex conjugation, the chang ...
into host plant cells after an injury site is sensed by the bacteria. These regions have features that allow the delivery of T-DNA into host plant cells, and can modify the host plant cell to cause the synthesis of molecules like
plant hormones
Plant hormone (or phytohormones) are signal molecules, produced within plants, that occur in extremely low concentrations. Plant hormones control all aspects of plant growth and development, from embryogenesis, the regulation of organ size, pat ...
(e.g.
auxins
Auxins (plural of auxin ) are a class of plant hormones (or plant-growth regulators) with some morphogen-like characteristics. Auxins play a cardinal role in coordination of many growth and behavioral processes in plant life cycles and are essenti ...
,
cytokinins
Cytokinins (CK) are a class of plant hormones that promote cell division, or cytokinesis, in plant roots and shoots. They are involved primarily in cell growth and differentiation, but also affect apical dominance, axillary bud growth, and le ...
) and opines and the formation of crown gall tumours.
Because the T-DNA region of the Ti plasmid can be transferred from bacteria to plant cells, it represented an exciting avenue for the transfer of DNA between
kingdoms
Kingdom commonly refers to:
* A monarchy ruled by a king or queen
* Kingdom (biology), a category in biological taxonomy
Kingdom may also refer to:
Arts and media Television
* ''Kingdom'' (British TV series), a 2007 British television drama s ...
and spurred large amounts of research on the Ti plasmid and its possible uses in bioengineering.
Nomenclature and classification
The Ti plasmid is a member of the
RepABC plasmid family found in Alphaproteobacteria.
These plasmids are often relatively large in size, ranging from 100kbp to 2Mbp. They are also often termed
replicons, as their replication begins at a single site. Members of this family have a characteristic ''repABC'' gene cassette.
Another notable member of this family is the root inducing (Ri) plasmid carried by ''A. rhizogenes'', which causes another plant disease known as hairy root disease.
A key feature of Ti plasmids is their ability to drive the production of opines, which are derivatives of various
amino acids
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
or
sugar phosphates, in host plant cells. These opines can then be used as a nutrient for the infecting bacteria, which
catabolizes the respective opines using genes encoded in the Ti plasmid.
Accordingly, Ti plasmids have been classified based on the type of opine they catabolize, namely:
nopaline-,
octopine- or mannityl-types, which are amino acid derivatives, or agrocinopine-type, which are sugar phosphate derivatives.
Historical discovery
The identification of ''A. tumefaciens'' as the cause of gall tumours in plants paved the way for insights into the molecular basis of crown gall disease.
The first indication of a genetic effect on host plant cells came in 1942-1943, where plant cells of secondary tumours were found to lack any bacterial cells within. However, these tumour cells did possess the ability to produce opines metabolized by the infecting bacterial strain. Crucially, the production of the respective opines occurred regardless of the plant species and occasionally only within crown gall tissues, indicating that the bacteria had transferred some genetic material to the host plant cells in order to allow opine synthesis.
However, how and to what extend did DNA transfer occur remained an open question. Adding ''A. tumefaciens'' DNA alone did not cause tumors in plants, while very little ''A. tumefaciens'' DNA was found to be integrated into the host plant cell genome. The addition of
deoxyribonucleases Deoxyribonuclease (DNase, for short) refers to a group of glycoprotein endonucleases which are enzymes that catalyze the hydrolytic cleavage of phosphodiester linkages in the DNA backbone, thus degrading DNA. The role of the DNase enzyme in ce ...
(DNases) to degrade DNA also failed to prevent the formation and growth of the plant tumors. These suggested that little, if any, of the ''A. tumefaciens'' DNA is transferred to the host plant cell to cause disease and, if DNA is indeed transferred from the bacteria to the plant, it must occur in a protected manner.
Subsequently,
oncogenic
Carcinogenesis, also called oncogenesis or tumorigenesis, is the formation of a cancer, whereby normal cells are transformed into cancer cells. The process is characterized by changes at the cellular, genetic, and epigenetic levels and abno ...
bacterial strains were found to be able to convert non-pathogenic bacteria into pathogens via the process of conjugation, where the genes responsible for virulence were transferred to the non-pathogenic cells. The role of a plasmid in this pathogenic ability was further supported when large plasmids were found only in pathogenic bacteria but not avirulent bacteria. Eventually, the detection of parts of bacterial plasmids in host plant cells was established, confirming that this was the genetic material responsible for the genetic effect of infection.
With the identification of the Ti plasmid, many studies were carried out to determine the characteristics of the Ti plasmid and how the genetic material is transferred from the ''Agrobacterium'' to the plant host. Some notable early milestones in the studies of Ti plasmids include the mapping of a Ti plasmid in 1978 and the studying of sequence similarity between different Ti plasmids in 1981.
Between 1980–2000, the characterization of the T-DNA region and the 'vir' region was also pursued. Studies into the T-DNA region determined their process of transfer and identified genes allowing the synthesis of plant hormones and opines. Separately, early work aimed to determine the functions of the genes encoded in the 'vir' region - these were broadly categorized into those that allowed bacterial-host interactions and those that enabled T-DNA delivery.
Replication, partitioning and maintenance
![RepABC gene cassette of Ti plasmids](https://upload.wikimedia.org/wikipedia/commons/d/d8/RepABC_gene_cassette_of_Ti_plasmids.png)
The replication, partitioning and maintenance of the Ti plasmid depends on the ''repABC'' gene cassette, which is mainly made up of three genes: ''repA'', ''repB'' and ''repC''. ''repA'' and ''repB'' each encode for proteins involved in plasmid partitioning, while ''repC'' encodes a replication initiator.
These genes are expressed from 4 different promoters located upstream of ''repA''. ''repE'' encodes for a small
antisense RNA
Antisense RNA (asRNA), also referred to as antisense transcript, natural antisense transcript (NAT) or antisense oligonucleotide, is a single stranded RNA that is complementary to a protein coding messenger RNA (mRNA) with which it hybridizes, and ...
and is located between ''repB'' and ''repC''.
Additionally, there is a partitioning site (''parS'') and an
origin of replication
The origin of replication (also called the replication origin) is a particular sequence in a genome at which replication is initiated. Propagation of the genetic material between generations requires timely and accurate duplication of DNA by semi ...
(''oriV'') present within the ''repABC'' cassette.
Replication of the Ti plasmid
The replication of the Ti plasmid is driven by the RepC initiator protein (), which possesses two
protein domains
In molecular biology, a protein domain is a region of a protein's polypeptide chain that is self-stabilizing and that folds independently from the rest. Each domain forms a compact folded three-dimensional structure. Many proteins consist of s ...
: an
N-terminal
The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the ami ...
domain (NTD) that binds to DNA and a
C-terminal
The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein is ...
domain (CTD). Mutational analyses have shown that without a functional RepC protein, the Ti plasmid is unable to replicate.
Meanwhile, the ''oriV'' sequence is around 150 nucleotides in length and is found within the ''repC'' gene.
Laboratory experiments have shown that the RepC protein binds to this region, suggesting its role as the origin of replication.
Therefore, while the complete process behind the replication of the Ti plasmid has not been fully described, the initial step of replication would likely depend on the expression of RepC and its binding to ''oriV''. Of note, the RepC protein only acts in ''cis'', where it only drives the replication of the plasmid it is encoded in and not any other plasmid also present in the bacterial cell.
Partitioning of the Ti plasmid
The
partitioning system of the Ti plasmid is similar to the ParA/ParB system used in other plasmids and bacterial chromosomes and is thought to act in the same way.
Mutations in either of the proteins RepA or RepB have resulted in a decrease in plasmid stability, indicating their role and importance in plasmid partitioning.
The ability of RepA to form filaments allows it to create a physical bridge along which DNA can be pulled to opposite poles of a dividing cell. Meanwhile, the RepB protein can bind specifically to the ''parS'' sequence, forming a complex with DNA that can be recognized by RepA.
This system is particularly important for the proper partitioning of the Ti plasmid, as the plasmid is only present in few copy numbers in the bacterial cell.
Maintenance of the Ti plasmid
The Ti plasmid is maintained at low copy numbers within a bacterial cell. This is partly achieved by influencing the expression of the replication initiator RepC.
When bound to
ADP, RepA is activated to work with RepB, acting as a negative
regulator of the ''repABC'' cassette.
The levels of RepC is therefore kept low within a cell, preventing too many rounds of replication from occurring during each cell division cycle. Furthermore, there is a small RNA known as RepE encoded between ''repB'' and ''repC'' that lowers the expression of ''repC''.
RepE is
complementary
A complement is something that completes something else.
Complement may refer specifically to:
The arts
* Complement (music), an interval that, when added to another, spans an octave
** Aggregate complementation, the separation of pitch-class ...
to RepC and will bind with the ''repC''
mRNA
In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein.
mRNA is ...
to form a double-stranded molecule. This can then block the
translational production of the RepC protein.
Separately, the expression of the ''repABC'' cassette and hence the copy number of the Ti plasmid is also influenced via a
quorum sensing
In biology, quorum sensing or quorum signalling (QS) is the ability to detect and respond to cell population density by gene regulation. As one example, QS enables bacteria to restrict the expression of specific genes to the high cell densities at ...
system in ''Agrobacterium''.
Quorum sensing systems respond to bacterial population densities by sensing a molecule, known as an autoinducer, that is produced by the bacterial cells at low levels and would build up to a threshold level when there is a high density of bacteria present.
In this case, the autoinducer is the N-3-oxooctanoyl-L-homoserine lactone (3-O-C
8-AHL) molecule, which is sensed by a regulator known as TraR.
When activated, TraR will bind to regions known as ''tra'' boxes in the ''repABC'' gene cassette's promoter regions to drive expression. Therefore, a high level of population density increases the number of plasmids present within each bacterial cell, likely to support pathogenesis in the plant host.
Features
Virulence operon
![Vir region of Ti plasmids](https://upload.wikimedia.org/wikipedia/commons/4/49/Vir_region_of_Ti_plasmids.png)
The expression of the ''vir'' region is usually repressed under normal conditions, and only becomes activated when the bacteria senses plant-derived signals from wound sites. This activation is necessary for the production of Vir proteins and the transfer of DNA and proteins into host plant cells.
VirA and VirG form a
two-component regulatory system
In the field of molecular biology, a two-component regulatory system serves as a basic stimulus-response coupling mechanism to allow organisms to sense and respond to changes in many different environmental conditions. Two-component systems t ...
within ''Agrobacterium''.
This is a type of sensing and signalling system found commonly in bacteria; in this case, they act to sense plant-derived signals to drive the expression of the ''vir'' region. During the sensing, VirA, a histidine sensor kinase, will become
phosphorylated
In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, wh ...
before passing on this phosphate group to the response regulator VirG. The activated response regulator VirG can then bind to a region of DNA known as the ''vir'' box, located upstream of each ''vir'' promoter, to activate the expression of the ''vir'' region.
One possible downstream functions of the sensing mediated by VirA and VirG is the directional movement, or
chemotaxis
Chemotaxis (from '' chemo-'' + ''taxis'') is the movement of an organism or entity in response to a chemical stimulus. Somatic cells, bacteria, and other single-cell or multicellular organisms direct their movements according to certain chemica ...
, of the bacteria towards plant-derived signals; this allows the ''Agrobacterium'' to move towards the wound site in plants. Furthermore, with the induction of the ''vir'' region, the transfer of T-DNA can be mediated by the Vir proteins.
The ''virB''
operon
In genetics, an operon is a functioning unit of DNA containing a cluster of genes under the control of a single promoter. The genes are transcribed together into an mRNA strand and either translated together in the cytoplasm, or undergo splic ...
is the largest operon in the ''vir'' region, encoding for 11 VirB proteins involved in the transfer process of T-DNA and bacterial proteins into host plant cells (see transfer apparatus below).
The ''virC'' operon encodes for two proteins: VirC1 and VirC2. These proteins influence the pathogenesis of the ''Agrobacterium'' towards different plant hosts, and mutations can reduce but not remove the virulence of the bacteria. Both the ''virC'' and ''virD'' operons can be repressed by a chromosomally encoded protein known as Ros.
Ros binds to a region of DNA that overlaps with the binding site of the VirG regulator, and therefore competes with VirG to control their expression levels.
Functionally, VirC1 and VirC2 promote the assembly of a
relaxosome
The relaxosome is the Multiprotein complex, complex of proteins that facilitates plasmid transfer during bacterial conjugation. The proteins are encoded by the tra operon on a fertility plasmid in the region near the origin of transfer, Origin of ...
complex during the conjugative transfer of T-DNA from the bacteria to the host plant cell.
This is an energy-dependent process mediated via their NTPase activity, and occurs as they bind to a region of DNA known as ''overdrive''.
As a result, they act to increase the amount of T-DNA strands produced. Following the production of the DNA strand to be transferred (transfer strand, T-strand), the VirC proteins can also help to direct the transfer strand to the transfer apparatus.
The ''virD'' operon encodes for 4 proteins: VirD1-D4. VirD1 and VirD2 are involved in the processing of T-DNA during conjugation to produce the T-strand; this is the single-stranded DNA molecule that is transported to the host plant cell (see transfer apparatus below).
During the processing, VirD1 will act as a
topoisomerase
DNA topoisomerases (or topoisomerases) are enzymes that catalyze changes in the topological state of DNA, interconverting relaxed and supercoiled forms, linked (catenated) and unlinked species, and knotted and unknotted DNA. Topological issues i ...
to unwind the DNA strands.
VirD2, a
relaxase A relaxase is a single-strand DNA transesterase enzyme produced by some prokaryotes and viruses. Relaxases are responsible for site- and strand-specific nicks in unwound double-stranded DNA . Known relaxases belong to the rolling circle replicati ...
, will then nick one of the DNA strands and remain bound to the DNA as it is transferred to the recipient cell.
Within the recipient cell, VirD2 will also work together with VirE2 to direct the transferred DNA to the recipient cell's nucleus. There are suggestions that VirD2 may be phosphorylated and dephosphorylated by different proteins, affecting its ability to deliver DNA. Conversely, little is known about VirD3, and mutational analyses have not provided any support for its role in the virulence of ''Agrobacterium''. Finally, VirD4 is a crucial part of the conjugation process, serving as a coupling factor that recognizes and transfers the T-strand to the transport channel.
The ''virE'' operon encodes for 2 proteins: VirE1 and VirE2. VirE2 is an effector protein translocated together with the T-strand into host plant cells. There, it binds to the T-strand to direct its delivery to the
nucleus
Nucleus ( : nuclei) is a Latin word for the seed inside a fruit. It most often refers to:
*Atomic nucleus, the very dense central region of an atom
*Cell nucleus, a central organelle of a eukaryotic cell, containing most of the cell's DNA
Nucle ...
of the host plant cell.
Part of this activity involves the presence of
nuclear localization sequence A nuclear localization signal ''or'' sequence (NLS) is an amino acid sequence that 'tags' a protein for import into the cell nucleus by nuclear transport. Typically, this signal consists of one or more short sequences of positively charged lysines o ...
s within the protein, which marks the protein and the associated DNA for entry into the nucleus. It also protects the T-strand from
nuclease
A nuclease (also archaically known as nucleodepolymerase or polynucleotidase) is an enzyme capable of cleaving the phosphodiester bonds between nucleotides of nucleic acids. Nucleases variously effect single and double stranded breaks in their ta ...
attack.
There is some speculation regarding the role of VirE2 as a protein channel, allowing DNA to move through the plant
cytoplasmic membrane
The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...
. On the other hand, VirE1 may be involved in promoting the transfer of the VirE2 protein into the host plant cell. It binds to the ssDNA-binding domain of VirE2, therefore preventing the VirE2 protein from prematurely binding to the T-strand within the bacterial cell.
''virF'' is a host specificity factor found in some but not all types of Ti plasmids; for example, octopine-type Ti plasmids possess ''virF'' but nopaline-types do not.
The ability of ''A. tumefaciens'' to induce crown gall tumours in certain plant species but not others has been attributed to the presence or absence of this ''virF'' gene.
The ''virH'' operon encodes for 2 proteins: VirH1 and VirH2.
A
bioinformatics
Bioinformatics () is an interdisciplinary field that develops methods and software tools for understanding biological data, in particular when the data sets are large and complex. As an interdisciplinary field of science, bioinformatics combi ...
study of the amino acid sequences of the VirH protein showed similarities between them and a superfamily of proteins known as
cytochrome P450
Cytochromes P450 (CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are ...
enzymes. VirH2 was then discovered to metabolize certain phenolic compounds detected by VirA.
Transfer DNA (T-DNA)
The T-DNA of ''Agrobacterium'' is approximately 15-20 kbp in length and will become integrated into the host plant genome upon its transfer via a process known as
recombination. This process utilizes preexisting gaps in the host plant cell's genome to allow the T-DNA to pair with short sequences in the genome, priming the process of
DNA ligation, where the T-DNA is permanently joint to the plant genome.
The T-DNA region is flanked at both ends by 24bp sequences.
Within the host plant cell's genome, the T-DNA of ''Agrobacterium'' is expressed to produced two main groups of proteins.
One group is responsible for the production of plant growth hormones. As these hormones are produced, there will be an increase in the rate of cell division and therefore the formation of crown gall tumors.
The second group of proteins are responsible for driving the synthesis of opines in the host plant cells. The specific opines produced depends on the type of the Ti plasmid but not on the plant host. These opines cannot be utilized by the plant host, and will instead be exported out of the plant cell where it can be taken up by the ''Agrobacterium'' cells. The bacteria possess genes in other regions of the Ti plasmid that allows the catabolism of opines.
Transfer apparatus
Transfer apparatuses encoded within the Ti plasmid have to achieve two objectives: allow the conjugative transfer of the Ti plasmid between bacteria and allow the delivery of the T-DNA and certain effector proteins into host plant cells. These are achieved by the Tra/Trb system and the VirB/VirD4 system respectively, which are members of the
type IV secretion system The bacterial type IV secretion system, also known as the type IV secretion system or the T4SS, is a secretion protein complex found in gram negative bacteria, gram positive bacteria, and archaea. It is able to transport proteins and DNA across t ...
(T4SS).
For the Ti plasmid and T-DNA to be transferred via conjugation, they must first be processed by different proteins, such as the relaxase enzyme (TraA/VirD2) and the DNA transfer and replication (Dtr) proteins. Together, these proteins will recognize and bind to a region known as the
origin of transfer An origin of transfer (''oriT'') is a short sequence ranging from 40-500 base pairs in length that is necessary for the transfer of DNA from a gram-negative bacterial donor to recipient during bacterial conjugation. The transfer of DNA is a critica ...
(''oriT'') in the Ti plasmid to form the relaxosome complex. For the T-DNA, a nick will be created at the T-DNA's border sequence, and the nicked T-strand will be transported to the cell membrane, where the rest of the transfer machinery is present.
Within the VirB/VirD4 system, the VirD2 relaxase is aided by the accessory factors VirD1, VirC1 and VirC2 while it processes the DNA substrate. Furthermore, the VirD2 relaxase and the VirC proteins will contribute to the delivery of the DNA strand to the VirD4 receptor at the cell membrane.
This receptor is an essential component of T4SSs, and is thought to energize and mediate the transfer of the DNA into the translocation channel between two cells. The table below summarizes the proteins encoded in the ''virB'' operon that makes up the translocation channel of the VirB/VirD4 system.
Uses in bioengineering
The ability of ''Agrobacterium'' to deliver DNA into plant cells opened new doors for plant
genome engineering
Genome editing, or genome engineering, or gene editing, is a type of genetic engineering in which DNA is inserted, deleted, modified or replaced in the genome of a living organism. Unlike early genetic engineering techniques that randomly inserts g ...
, allowing the production of
genetically modified plants
Genetically modified plants have been engineered for scientific research, to create new colours in plants, deliver vaccines, and to create enhanced crops. Plant genomes can be engineered by physical methods or by use of '' Agrobacterium'' for the ...
(transgenic plants). Proteins involved in mediating the transfer of T-DNA will first recognize the border sequences of the T-DNA region. Therefore, it is possible for scientists to use T-DNA border sequences to flank any desired sequence of interest - such a product can then be inserted into a plasmid and introduced into ''Agrobacterium'' cells. There, the border sequences will be recognized by the transfer apparatus of ''A. tumefaciens'' and delivered in a standard manner into the target plant cell.
Moreover, by leaving behind only the border sequences of the T-DNA, the resulting product will edit the plant genome without causing any tumours in plants. This method has been used to modify several crop plants, including rice, barley and wheat. Further work have since extended the targets of ''A. tumefaciens'' to include fungi and human cell lines.
Similar plasmids
Root-inducing (Ri) plasmid
Symbiotic (sym) plasmids of Rhizobia
See also
*
Mary-Dell Chilton
*
Jeff Schell
Jozef Stefaan "Jeff", Baron Schell (20 July 1935 – 17 April 2003) was a Belgian molecular biologist.
Schell studied zoology and microbiology at the University of Ghent, Belgium. From 1967 to 1995 he worked as a professor at the university. Fro ...
*
Marc Van Montagu
Marc, Baron Van Montagu (born 10 November 1933 in Ghent) is a Belgian molecular biologist. He was full professor and director of the Laboratory of Genetics at the faculty of Sciences at Ghent University (Belgium) and scientific director of the ...
References
External links
Agrobacterium tumefaciens plasmid pTi-SAKURA, complete sequenceTi Plasmid Genetic MapCrown gall disease
{{DEFAULTSORT:Ti Plasmid
History of biotechnology
Plasmids