Since 2001, my group studies the molecular and biochemical mechanisms underlying disease -resistance and -susceptibility in plants. We want to understand how the immune system of a plant allows it to recognise a pathogen and mount effective defence responses. Furthermore, we want to elucidate how pathogens manipulate their hosts and manage to evade its immune system.
As model crop, we use tomato because of its great genetic tools and its importance for Dutch agriculture. Tomato has many natural enemies and one of them is the root-invading soil-borne pathogen Fusarium oxysporum, the causal agent of Fusarium wilt disease. Resistance to fusarium can be conferred by Resistance genes. These genes encode immune receptors that recognize specific proteins secreted by the fungus. Our aim is to understand how NLR-type immune receptors function in disease resistance. Biochemically we have shown that these proteins act as nucleotide-operated molecular switches. In collaboration with the Cann laboratory (Durham UK) we found that these proteins can bind and bend DNA in vivo, and that in planta they bind DNA once activated. In an NWO funded VICI project we study the role of DNA binding by NLR proteins in plant immunity.
Although Fusarium oxysporum is infamous for being a devastating pathogen, many strains are actually endophytes that enhance plant resilience to biotic and abiotic stresses. Current research aims at resolving how endophytes evade host resistance while boosting plant immunity, and to elucidate how endophytes differ from pathogens.
Disease resistance can also be conferred by a lack of compatibility with a given pathogen. To unravel this mechanism, we focus on the identification of compatibility/susceptibility genes of the host by screening for protein targets that are manipulated by a pathogen. Upon infection Fusarium oxysporum secretes many small proteins in the xylem sap of the host. Many of these Six (Secreted In Xylem) proteins, such as Six3, Six5 and Six6, are important for disease development, like. We use these Six proteins to identify their planttargets and identified genes whose knockout result in increased disease resistance. Identification of these susceptibility genes increases our understanding on how a pathogen manipulates its host and providing new leads to combat diseases
Current members of the research team.
Margarita Simkovicova PhD student - "Combating Vascular Diseases: Identifying the Guardians of the Xylem Sap", Collaboration with ENZA zaden, funding by ENZA and NWO-VICI program
Thomas Aalders PhD Student- TOPLESS a novel S gene: Unravelling the manipulation of Topless by a conserved effector from Fusarium oxysporum", funding by NWO talent program:
Mila Blekemolen PhD student - "Elucidating the molecular mechanism underlying the virulence and avirulence functions of the Fusarium Avr2/Six5 effector pair" Funding from NWO VICI program and UvA.
Dr Nico Tintor Postdoc - "The role of effector uptake in plant immunity." ollaboration with ENZA zaden, funding by ENZA and NWO-VICI program
Dr Marijn Knip, Postdoc - VICI project: Linking plant immunity and DNA damage.
Dr Manon Richard, Postdoc - VICI project: Linking DNA binding of plant NLR proteins to plant immunity.
Machiel Beijaert, Technician - VICI project: supporting the VICI project in various ways.
Dr Francisco de Lamo Ruiz, PhD student - ETN Horizon2020 : How do endophytes evade host resistance while enhancing immunity?
Dr Maria Constantin, PhD student - ETN Horizon202: How do endophytes differ from pathogens?
Dr Lingxue Cao, PhD student - CSC grant: Elucidating the molecular mechanism underlying the virulence and avirulence functions of the Fusarium Avr2/Six5 effector pair,
Dr Xiaotang Di, PhD student - CSC grant : The Avr2 effector protein from Fusarium as a guide to unravel plant innate immunity.
Dirk-Jan Valkenburg, Technician: involved in various ongoing projects in the group.
Dr Hanna Richter, Technician: involved in all ongoing projects in the group.
ir. Lisong Ma, PhD student: Analysing the intrinsic functions of Avr2 and its perceival by the resistance protein I-2.
Dr Fleur Gawehns, PhD student - CBSG2012: Functional characterisation of Fusarium secreted effector proteins in disease and resistance
Dr ir. Ewa Lukasik, PhD student -Bioexploit: "Role of the ATPase activity of the NBS domain of R proteins and the identification of interacting proteins.
drs Vladimir Krasikov, Postdoc -UvA: Identifying the role of the Xsp10 protein for resistance and disease to Fusarium oxysporum.
dr. ir. Harrold van den Burg, Postdoc, NWO Veni: Eludidating the role of SUMO modification in plant defence signalling.
ing Marianne de Vroomen Technician, involved in most ongoing projects.
Drs Mobien Kasiem PhD student: PhD student: Structure and function of tomato disease resistance proteins.
Dr Gerben van Ooijen PhD student -NWO open program: Structure and function of tomato disease resistance proteins.
Dr Klaas Jan de Vries, Postdoc - CBSG 2008: Targeted proteomics of signalosomes mediating pathogen resistance.
Dr Wladimir Tameling PhD student: Disease resistance proteins of the NBS-LRR class, molecular switches of plant defence.
Dr Sergio de la Fuente van Bentem PhD student: Unfolding plant disease resistance, the involvement of HSP90 and its co-chaperone PP5 in I-2 mediated signalling.
Dr Jack Vossen, Postdoc: Characterisation of the I-2 signalosome.
Dr Sandra Elzinga, Postdoc: Characterisation of the Mi-1 signalosome.
Selection from the last ten years
Frank Takken (1969) is interested in how plants defend themselves against pathogens. Plants are able to sense the presence of invading microbes. Recognition subsequently results in activation of the plant innate immune system. In this process, resistance proteins play a key role as they mediate pathogen recognition and trigger the activation of downstream signaling cascades that halt the pathogen and thereby prevent disease. An example of a succesfull immune response is shown in the figure below where the tomato Immunity-2 ( I-2) gene halts ingress of the pathogenic fungus Fusarium oxysporum.
Resistance genes come in different flavors, but the majority encodes intracellular tri-partite proteins that contain a central nucleotide-binding domain. One of Frank's major research interests is the role the distinct domains in these proteins have for their function. Structure-function analysis in combination with 3D modeling of the different subdomain is used to predict mutations that will have specific effects on the activity of these proteins. These mutants are subsequently analyzed for altered biochemical properties, differences in inter- and intramolecular interactions as well as for their effect on disease resistance.
To examine how resistance proteins activate downstream signaling it is essential to know their interacting partners. Using various screens, candidate interacting proteins, and recently also DNA, have been identified and these interactors are analyzed for their involvement in plant defense. Part of this research is funded by an NWO VICI grant that was awarded in 2015. Besides resistance genes, I also have a long standing interest to resolve the molecular basis of host susceptibility and the induced resistance responses triggered by biocontrol fungi.
Frank is appointed as Associate professor in the Molecular Plant Pathology group at the Swammerdam Institute for Life Sciences and was from 2012-2019 Scientific Advisor for Scienza Biotechnology. Previously he worked as postdoc at the Phytopathology group at Wageningen University. During this time he worked on a self-written project at the biotech company Keygene NV in Wageningen. In that project he focused on the identification of genes that are transcriptionally regulated during the onset of plant defense signaling. He received his PhD in 1999 from the Free University of Amsterdam for his pioneering work on the isolation of resistance genes from tomato.