MSc in Biological Sciences Research

Pathogens secrete small proteins called effectors or virulence factors which are important for the successful invasion of the host. These effectors act by compromising the host immunity. Powdery mildews are economically important obligate fungal pathogens of many crops, including wheat, barley, pea strawberry or zucchini. Powdery mildew expresses and secretes many small proteins, most of them of unknown functions, except for the fact that they make the pathogen virulent. The production of these are regulated at the early stage of infection. To understand their function, we will be addressing one or some of the following questions:

When and where are they expressed? And what are the transcription factors regulating them?

Which of the plant host proteins do they target?

Are they species specific?

Are they required for a successful infection?

Molecular and proteomic approaches will be used to investigate the role of powdery mildew effector proteins of this plant pathogen during infection of barley by its powdery mildew.

Research pages - Dr Bindschedler

The aim of this project is to develop high output workflow for gene silencing of obligate plant pathogenic fungi with an ultimate goal of controlling plant diseases causing rust and powdery mildews.

RNA interference (RNAi) is a powerful technique to investigate gene function by down regulating the expression of a particular gene in vivo (i.e. gene silencing).

Large scale RNAi strategies were possible through the design of synthetic siRNAs in mammalian systems or artificial microRNAs in plants but depend on cloning and protoplasts production.

Newer methods to adapt RNAi to plant systems have emerged using either cell permeable peptides to use direct siRNA or oligodeoxynucleotides (ODN) molecules uptake in whole plants or leaves.

These silencing screening tools are instrumental for the designing of resistant genome edited plants.

Research pages - Dr Bindschedler

Plant growth and crop productivity is intimately linked to the efficiency of light capture and to the balanced storage and utilisation of assimilates. The evolutionary conserved TOR-S6K signalling pathway functions to adjust the rate of protein synthesis to demands (Deprost et al. (2007) EMBO Rep 8:864-870.).

Cell proliferation is repressed upon carbon starvation, and we have shown that S6K1 is playing a role in this process (Henriques et al. (2010) EMBO J 29:2979-93.). We have also shown that exposure of etiolated seedlings to light rapidly revert starvation and leads to activation of protein synthesis and cell proliferation in shoot apex.

Light has a direct input into cell proliferation through DET1 and COP1 which regulate the balance between transcriptional activator/repressor; E2FB/E2FC (Lopez et al (2008) Plant Cell 20:947-68.). Cell proliferation adjusted to available sucrose through regulating the expression, translation and protein stability of D-type cyclins and so RBR phosphorylation and leads to the release of E2FB to activate proliferation (Magyar et al (2012) EMBO J. 31:1480-93.).

On the other hand, E2FA forms a stable repressor complex with RBR to maintain the meristem, while E2FC appears to be involved in induction of genes involved in metabolism, light and circadian rhythm (deJager et al. (2009) PMB 71(4-5):345-65.). The central question of this project: how carbon balance is connected to the regulation of growth and cell proliferation.

Research pages - Professor Bogre

One major consequence of the global changes in climate is an uneven distribution of freshwater, leading to drought in large areas worldwide. This has already had a strong influence on agricultural productivity.

Our current understanding of plant adaptation to drought stress is limited to survival mechanisms, but little is known about how mild drought condition restrains plant productivity and yield. We have discovered a drought induced MAPK signalling pathway that restrains plant growth through multiple mechanisms; i) by regulation auxin transport, ii) regulating cell proliferation.

The overall aim of the proposed research is to identify cell cycle-regulatory targets of the drought-responsive MAPK signaling pathway, and link these to the growth adaptation of plants under drought stress conditions. To do this we will perform: (ii) computational predictions of MAPK substrates involved in cell cycle regulation, (iii) targeted approaches to test MAPK phosphorylation of key regulators in plant growth regulation, the RBR transcriptional repressor complex.

Research pages - Professor Bogre

Bumblebees are the unfortunate poster-child for insect declines around the globe. As well as their intrinsic value, they are essential for wildflower and crop pollination, making their conservation essential. In Argentina, populations of the world’s largest bumblebee (Bombus dahlbomii) have collapsed dramatically, and this is linked to the invasion of South America by European bumblebees that are used for commercial pollination. One way to protect remaining threatened populations of B. dahlbomii may be to manage invasive bumblebees during the mating season. This project will determine the sexual chemicals of native and invasive bumblebee males, and design and test pheromone-based male traps to control invasive bumblebee populations. It will require fieldwork in Argentina.

This masters project is a collaboration with Dr Marina Arbetman (CONICET, Argentina), a world-leader in the conservation of Bombus dahlbomii, and will involve lab and field work in both Argentina and the UK.

Research pages - Professor Brown

Pollinators, like bumble bees, are essential to natural ecosystems and human food supplies, but they are facing declines around the world. Parasites have been suggested to be behind some of these declines. Consequently, understanding how bees protect themselves against parasites is an important question. One way that bees might be able to protect themselves is by self-medication – taking advantage of plant-produced chemicals to control parasites. This project will use bumblebees, a gut parasite, and nectar chemicals to ask if, how, and when bumblebees use plant chemicals to protect themselves against parasites.

This masters project will be associated with an on-going NERC-funded research project that is a collaboration between Royal Holloway and the Royal Botanic Gardens Kew.

Research pages - Professor Brown

Pollinators, like bumble bees, are essential to natural ecosystems and human food supplies, but they are facing declines around the world. Pesticides have been suggested to be a major driver of these declines. However, whether the impacts of pesticides on bees is limited to agricultural areas or occurs in adjacent natural areas, or other areas, is largely unknown. This project will investigate the exposure of pollinators to pesticides in non-agricultural habitats to understand whether pesticides threaten pollinators more broadly than currently assumed.

This masters project will be associated with an on-going EU-funded research project called WildPosh (https://www.wildposh.eu/).

Research pages - Professor Brown

This project will characterise a number of novel agonists at NMDA receptors using molecular biology and recording glutamate evoked inward currents from oocytes injected with mutant NMDARs under two-electrode voltage clamp configuration. The project will involve molecular techniques such as subcloning, site-directed mutagenesis, PCR and in vitro cRNA synthesis, injection of cRNA into Xenopus oocytes and two-electrode voltage clamp electrophysiology.

Research page - Dr Chen

RNA editing is a process by which specific nucleotides are modified following gene transcription and disruptions in these processes have been linked to certain neurodegenerative conditions. We have developed a number of genetic tools to manipulate RNA editing and would like to explore their consequences on cell function. This project would involve mammalian tissue culture, RNA extraction, cell transfection and RT-PCR.

Research page - Dr Chen

Work consists of innovative bacterial delivery systems for mucosal vaccination (i.e. against malaria or TB). Due to the dynamics of our projects, they are ongoing and subject to change on a regular basis and cannot be specified in advance.

Research pages - Professor Cutting

Healthy plants, like all higher organisms, host an extensive commensal microbial community or microbiome. Non-pathogenic microbes in many cases benefit the host. In plants, both the leaf microbiome, the phyllosphere, and the root microbiome, the rhizosphere, contain a wide range of bacterial and fungal species, including some that have been shown to play a range of roles in disease prevention. Changes in the microbiome can, therefore, have important effects on agricultural yield and microbial supplementation offers a real option for biological control of disease, reducing the need for fungicides. Understanding the rules of establishment of microbial supplements within the microbiome is currently a key knowledge gap, with many potential biological control agents failing to establish in the field under real agricultural conditions. This project will use a metabarcoding approach to analyse the impact of a range of biotic and abiotic stresses experienced by plants in the field on the phyllosphere microbiome and to try and establish the key elements that define a resilient microbial community. We will analyse the effects of both environmental and agricultural treatments. Effects on the microbiome of abiotic factors such as light, drought stress, plant immune responses and even internal plant circadian rhythms will also be tested. This project will also investigate the potential for probiotic treatment / microbiota transfer to help restore microbial homeostasis using synthetic communities (SynComs) cultured from microbes native to healthy untreated plants.

References:

Vincent et al. 2022, Front in Microbiol. 13:809940)

Gadhave et al. 2018, Microb Ecol 76:741-50

Research pages - Dr Paul Devlin

The greatest advantage of a circadian clock in plants is the accurate prediction of the timing of dawn and dusk. On the other hand, dawn and dusk also keep the clock in tune with the environment by resetting the clock forward or back slightly each day.  This involves a fine balance and so plants have a range of photoreceptors that interact to convey accurate environmental information.

This project will look at integration of red and blue light signals as their relative importance changes through the course of a day. It will focus on the interaction of signals from the red light-regulated transcription factors, FHY3 and FAR1, and the blue light-regulated transcription factors HY5 and HYH.

References:

Rhodes et al. 2022, Front Plant Sci.13:862387

Liu et al. 2020, Plant Cell 32(5):1464-78

Li et al., 2011, Nature Cell Biology, 13: 616-622

Research pages - Dr Paul Devlin

The project aims at elucidating several aspects of the control of plant defences and to identify environmentally friendly forms of plant protectants and phytopharmaceuticals, leading to enhanced crop yields and solutions for animals and human health.

Host processes and components required for the reproduction of plant microbes to uncouple stress-induced growth in plants are studied to open the possibility to engineer crops to gain ‘natural immunity’. Host processes linked with microbial growth to uncover cellular and metabolic changes associated with their demands will be elucidated This research will also further our understanding of biomass production and its regulation in response to stress to improve cell wall accessibility in biofuel feedstocks.

My projects span from experimental Sciences to BIG DATA dry projects and offer the opportunity to become familiar with approaches and techniques of wide applicability such as high-throughput functional genomics/ bioinformatics, epigenetics, as well as molecular biology and protein engineering and sustainable green technology.

Latest/ relevant References

Krasauskas et al 2023 JXBot 75:180; Vincent et al 2022, BMC Biology 20, 83; Bomer, Perez Salamo et al 2020. New Phytol 229:2120; Perez Salamo et al 2018 Annual Plant Reviews 2, p. 1-65; Noir et al, 2013, Plant Physiology 161: 1930-1951; Balbi and Devoto, 2008, New Phytologist, 177: 301-318

Research pages - Professor Devoto

Pathways with potential to produce therapeutic drugs will be manipulated with the dual aim of developing a greater understanding of the metabolism involved, that is often related to plant defence, and to develop small molecules or precursors for new medicines. Success in manipulating the targeted metabolic pathways will be analyzed through a novel functional screening system. The analysis of diverse plant lines will improve the understanding of key pathways leading to the production of economically important compounds acting as toxins, antimalarial, or antineoplastic drugs in planta. This project will also contribute to identifying the link between plant growth and responses to stress and will lead to the discovery of regulators with the potential to engineer stress signalling pathways.

My projects span from experimental Sciences to BIG DATA dry projects and offer the opportunity to become familiar with approaches and techniques of wide applicability such as high-throughput functional genomics/ bioinformatics, epigenetics, as well as molecular biology and protein engineering and sustainable green technology.

Latest/ relevant References

Krasauskas et al 2023 JXBot 75:180; Vincent et al 2022, BMC Biology 20, 83; Bomer, Perez Salamo et al 2020. New Phytol 229:2120; Perez Salamo et al 2018 Annual Plant Reviews 2, p. 1-65; Noir et al, 2013, Plant Physiology 161: 1930-1951; Balbi and Devoto, 2008, New Phytologist, 177: 301-318

Research pages - Professor Devoto

Understanding the mechanism by which chromatin remodelling and/or hormone signalling components work in regulating cell growth in response to the stress, will contribute to increase fitness potential (and biomass or high value chemicals, accumulation) of plants during stress, a critical issue for a sustainable agriculture development. Using high-throughput functional genomics, the role of newly identified molecular components will be established. This project will contribute to identifying the link between plant growth and responses to stress and will lead to the discovery of regulators with the potential to engineer stress signalling pathways. The knowledge accumulated here will be applied to crops.

My projects span from experimental Sciences to BIG DATA dry projects and offer the opportunity to become familiar with approaches and techniques of wide applicability such as high-throughput functional genomics/ bioinformatics, epigenetics, as well as molecular biology and protein engineering and sustainable green technology.

Latest/ relevant References

Krasauskas et al 2023 JXBot 75:180; Vincent et al 2022, BMC Biology 20, 83; Bomer, Perez Salamo et al 2020. New Phytol 229:2120; Perez Salamo et al 2018 Annual Plant Reviews 2, p. 1-65; Noir et al, 2013, Plant Physiology 161: 1930-1951; Balbi and Devoto, 2008, New Phytologist, 177: 301-318

Research pages - Professor Devoto

Plant and microbial natural products have been utilised by human civilisation for millennia, providing vital medicines and essential dietary components. More recently bioactive compounds from plant sources have been used in cosmetics, as health supplements and are important components of food and feedstuffs. Phytochemicals are also important industrial raw materials and high-value fine chemicals. Despite the significant investments made in combinatory chemical synthesis, these platforms have not delivered the desperately needed new activities and/or sources of complex structures found in nature. Chemical synthesis is also expensive and typically associated with chemical refineries using non-renewable energy sources and byproducts.

Terpenoids or isoprenoids are a class of compounds within which specific compounds have anti-cancer activity, confer health benefits, are natural colorants, and feed supplements. The present markets for isoprenoid compounds such as ketocarotenoids which are natural colorants and antioxidants are worth over $1 billion per annum, with demand far exceeding supply (Marz, 2006, Business report. Global Market for carotenoids, Norwalk CT, USA: Business Communications Company).

In the proposed project the applicant will (i) characterise existing transgenic plants and microorganisms producing high value bioactive natural products using modern omic technologies and (ii) generated and evaluate new biosources of these compounds using synthetic biology approaches.

Research pages - Professor Fraser
Project pages - www.metapro.eu and www.multibiopro.eu

Banana (Musa spp.), Cassava, Yam and Sweet potato are one of the top ten staple foods in the developing world and a target for international development to genetically enhance these crops. The proposed project will augment on-going plant breeding programmes in Africa, Asia and South America, designed to improve consumer traits in banana fruit. The applicant will perform metabolite profiling on well characterised segregating populations and integrate this metabolite information with genetic data. QTL underlying traits and candidate genes will then be characterised in transient and other fruit systems. The applicant will be provided with a unique opportunity to interact with research programmes aimed at combating food insecurity and poverty in developing countries.

Research pages - Professor Fraser
Project pages - www.metapro.eu and www.multibiopro.eu

Plants rely on a diverse assemblage of micro-organisms (microbiome) to fulfil their life cycle, but we still ignore the composition, diversity, and function of the seed microbiome. This is a critical knowledge gap because seeds are the most vulnerable stage in the plant demographic cycle. As a result, low seed germinability is the main factor hampering rewilding, i.e., forest expansion over formerly managed areas depleted of vegetation. Rewilding of plant communities is highlighted by the IPBES as the main nature-based solution to halt biodiversity decline and mitigate the impacts of climate change. This project aims to test whether seed germinability of trees relies on the species composition of the seed microbiome, specifically on seed bacteria. community. Specifically, we will test if animal-dispersed seeds secure bacterial communities that enhance seed germination from the guts of their mutualistic frugivores, in turn providing most suitable conditions to germinate and establish successfully. The main goals main goals are: (i) Describing the species composition and function of the seed microbial communities -based on 16S rDNA- for tree species (N~35) native to UK; (ii) Elucidating whether seed microbiomes impact seed germinability and, if so, identifying the combination of micro-organisms that attain higher germinability and recruitment under different simulated environmental conditions, including drought; (iii) Investigating the role of frugivores in shaping the composition and function of the seed microbiome; (iv) Engineering synthetic seed microbial communities that enhance seed germination and long-term establishment of native trees. Overall, this study will provide scientific evidence to initiate forest improved regeneration trials based seeds coated with synthetic seed microbial communities to trigger forest recovery (knowledge transfer).This project will address the following skill gaps: (i) Designing seed germination trials across multiple tree species native to the UK; (ii) Optimize and apply DNA extraction protocols (bacterial 16S rDNA); (iii) Apply statistical tools to characterize and compare seed microbial communities; and (iv) Learn how to engineer seed microbial communities; v) Plotting informative figures summarizing most relevant results (to acquire some basic knowledge on infographics); and vi) Draft a scientific manuscript aimed to publish main relevant results of this project.

Research page - Dr Garcia

Daniel Janzen hypothesized that the breadth of the thermal niche of organisms determines their distribution ranges as well as the turnover of species across altitudinal gradients (Janzen 1967). This predicts that narrow climatic variation of the tropics determines narrow thermal niches of tropical species, which might hamper their expansion across altitudinal or latitudinal gradients. This hypothesis has been confirmed for insects, birds, mammals, and lizards, but we still ignore whether it also applies to plants. This knowledge gaps hampers our understanding of plant responses to increasing warming conditions and limit our ability to forecast their ability to persist in a changing world. This project aims to test the hypothesis that tropical species show narrower thermal niches compared to non-tropical species. By doing so we will investigate the role of thermal niche in driving plant responses to increasing warming. We will use a combination of data bases to depict the breath of the climatic niche and to gather ancillary data on key functional traits such as dispersal and pollination mode, lifespan, phenology, and phenotypic traits. This project will address the following skill gaps: (i) Designing and applying a pilot study to identify and avoid common statistical pitfalls (pseudorreplication, zero inflated data, low statistical power, phylogenetic bias); (ii) Based on the feedback from the pilot study, defining a data frame with the suitable number and type of variables and records to be analysed with R; (iii) Gathering data from a combination of data bases (books, guides, climate data bases, and online repositories); and (iv) Applying multivariate tools to depict and compare the breath of the climate niche of plants and phylogenetic regressions to identify main functional traits driving plant responses; v) Plotting informative figures summarizing most relevant results (to acquire some basic knowledge on infographics); and vi) Draft a scientific manuscript aimed to publish main relevant results of this project.

Research page - Dr Garcia

Plants rely on a diverse assemblage of micro-organisms (microbiome) to fulfil their life cycle, but we still ignore the composition, diversity, and function of the seed microbiome. This is a critical knowledge gap because seeds are the most vulnerable stage in the plant demographic cycle. As a result, low seed germinability is the main factor hampering rewilding, i.e., forest expansion over formerly managed areas depleted of vegetation. Rewilding of plant communities is highlighted by the IPBES as the main nature-based solution to halt biodiversity decline and mitigate the impacts of climate change. This project aims to test whether seed germinability of trees relies on the species composition of the seed microbiome, specifically on seed bacteria. community. Specifically, we will test if animal-dispersed seeds secure bacterial communities that enhance seed germination from the guts of their mutualistic frugivores, in turn providing most suitable conditions to germinate and establish successfully. The main goals main goals are: (i) Describing the species composition and function of the seed microbial communities -based on 16S rDNA- for tree species (N~35) native to UK; (ii) Elucidating whether seed microbiomes impact seed germinability and, if so, identifying the combination of micro-organisms that attain higher germinability and recruitment under different simulated environmental conditions, including drought; (iii) Investigating the role of frugivores in shaping the composition and function of the seed microbiome; (iv) Engineering synthetic seed microbial communities that enhance seed germination and long-term establishment of native trees. Overall, this study will provide scientific evidence to initiate forest improved regeneration trials based seeds coated with synthetic seed microbial communities to trigger forest recovery (knowledge transfer). This project will address the following skill gaps: (i) Designing seed germination trials across multiple tree species native to the UK; (ii) Optimize and apply DNA extraction protocols (bacterial 16S rDNA); (iii) Apply statistical tools to characterize and compare seed microbial communities; and (iv) Learn how to engineer seed microbial communities; v) Plotting informative figures summarizing most relevant results (to acquire some basic knowledge on infographics); and vi) Draft a scientific manuscript aimed to publish main relevant results of this project.

Research page - Dr Garcia

Microbes interact in various ways, for instance they can release antibiotics to stave off competitors, or they can release substances which help other microbes take up iron from the environment. In this way basic ecological interactions, such as competition or mutualisms can be realised in very simple organisms. This project aims to develop simple models for the interaction of microbes. Once such a model is formulated and analysed, it can then be used to study the evolution of microbes in a theoretical fashion. This project will concentrate on the production of siderophores, which allow microbes to interact through the production of a public good. This is a theoretical project that will require some experience and interest in mathematical modelling.

Research Pages - Vincent Jansen

Fungi interact with plants in various ways, for instance as pathogen, but they can also engage in a mutualistic interaction through the formation of mycorrhizas. They can release antibiotics to stave off competitors, or they can release substances which help other microbes take up iron from the environment. In this way basic ecological interactions, such as antagonisms or mutualisms can be realised. This project aims to develop simple models for the plant-fungal interaction of microbe. Once such a model is formulated and analysed, it can then be used to study the evolution of microbes in a theoretical fashion. This is a theoretical project that will require some experience and interest in mathematical modelling

Research pages - Professor Jansen

Several deciduous tree species retain all or some senesced leaves on branches through much of winter, a phenomenon called leaf marcescence. This project will explore the frequency and phenology of marcescence in several tree species as well as its potential functional significance. It has been proposed that benefits of retaining dead leaves over winter might include protection of buds from frost, deterrence of herbivores, provision of overwintering habitat for predators such as spiders, or improvement of nutrient resorption. The project will test some of the above hypotheses.   

References:

Heberling, J. M., and Muzika R.M. (2023). Not all temperate deciduous trees are leafless in winter: the curious case of marcescence. Ecosphere 14: e4410. 

Pearse, I.S. et al. (2020) Generalising indirect defence and resistance of plants. Ecology Letters 23: 1137-1152.

Research pages - Professor Koricheva 

Concern has arisen that managed honeybees may have unintended negative impacts on native wild bees, which are important pollinators in both agricultural and natural ecosystems. These negative effects may arise because of competition for floral and nesting resources, changes in plant communities, including the spread of exotic plants and decline of native plants, and transmission of pathogens. This project will review the evidence of effects of managed honeybees on wild bees through a meta-analysis, which is a set of statistical methods designed to combine the results from independent studies on the same topic. Training in meta-analysis will be provided.

References:

Iwasaki, J. M. and K. Hogendoorn (2022). Mounting evidence that managed and introduced bees have negative impacts on wild bees: an updated review. Current Research in Insect Science 2: 100043.

Mallinger RE, Gaines-Day HR, Gratton C (2017) Do managed bees have negative effects on wild bees? A systematic review of the literature. PLoS ONE 12: e0189268

Wojcik V.A. et al. (2018). Resource competition between honey bees and wild bees: is there clear evidence and can we guide management and conservation? Environmental Entomology 47: 822–833.

Research pages - Professor Koricheva 

This Masters is part of the Royal Holloway Schools’ Biodiversity Project and will investigate how working with children in their school grounds affects their connection to nature and science attainment, particuarly in biology but also more generally. You will visit children weekly and work with them on projects to monitor species or create habitats in their grounds. The ability to work with children and to handle a wide range of species is essential. You will learn social science surveying and analysis techniques as well as identification, surveying and data collection techniques suited to citizen science projects centred around children.

Research pages - Deborah Harvey

One of the goals of ageing research is to identify compounds that can extend lifespan and/or improve physical and cognitive performance in old age. The research of the last 20 years revealed a high level of conservation of genetic pathways and biochemical processes that regulate lifespan in organisms as diverse as yeast, worms, flies and humans. The fruit fly Drosophila, in particular, emerged as a pre-eminent model system for studying changes that occur during both normal and pathological ageing (~75 per cent of the genes that cause disease in humans are also found in the fruit fly!). The advantages of Drosophila include their relatively low cost, ease of use and a range of powerful tools available for their genetic manipulation.

Our Department recently identified several compounds with possible pro-longevity effects. The aim of this project is to assess the effect of these compounds during healthy ageing and in various Drosophila models of human diseases. The initial lifespan studies will be followed by an array of molecular, biochemical, imaging and functional analyses.

Research pages - Dr Hrvoje Augustin

We use the fruit-fly Drosophila to study different aspects of human neurodegenerative diseases such as Motor neurone disease, Parkinson’s disease, Frontotemporal dementia and others. Our main goals are to a) understand the molecular underpinning of these disorders, and b) identify novel molecular targets and therapeutic approaches for future treatments. The most promising genetic or pharmacological interventions identified in flies can then be tested in suitable mouse disease models.

Research pages - Dr Hrvoje Augustin

The aim of this project is to determine the mechanisms which are underlying seed enhancement technologies to achieve rapid and uniform germination and seedling establishment. These technologies include seed priming, sorting, pelleting and the inclusion of various additives. Examples for the effects include the release of seed dormancy of vegetable and flower seeds, the control of aging processes during sugarbeet and onion seed storage and the benefits of priming to improve abiotic stress responses and vigour during germination and pre-emergence seedling growth (see projects on our PURE website below). The underlying mechanisms include regulation by altered hormonal contents and signalling and epigenetic changes leading to distinct transcriptome expression patterns. Very little is known about these mechanisms and therefore the optimisation of the seed enhancement technologies and their application to specific crop species is hampered. In the project we will investigate crop seed enhancement technologies with modern molecular, biochemical, microscopical and biophysical methods to understand how embryo growth, dormancy release and germination speed, uniformity and vigour are improved. This project is at the interface of fundamental and applied seed biology and engineering.

For enquiries about Projects in the Leubner laboratory, please contact Prof Gerhard Leubner.

Research pages - Professor Leubner

Project pages 'The Seed Biology Place'

The sustainable intensification of food production necessary to feed the world’s growing population will only be achievable if crop harvest losses due to heat stress and competition with weeds are minimised. About ten per cent of crop production is currently lost to weeds and this loss would be far greater without the use of herbicides. However, the continued effectiveness of herbicide technology is threatened by the rapid advance of weed biotypes that are resistant to herbicides. The problem of effective weed control is most severe in annual field crop systems and with annual weeds which emerge at the same time as the crop seedlings. These problem weeds owe their success, at least in part, to the formation of large and persistent soil seed banks. Thus there is considerable potential for novel weed control solutions through engaging a deeper understanding of the molecular mechanisms of weed seed germination and survival. In the project we will focus on hormone-related mechanisms which mediate the environmental responses of weed seeds. Seed hormones will be quantified and the expression of corresponding genes analysed in the seeds of a variety of noxious weeds and in response to temperature as environmental factor. This project is in collaboration with Syngenta and at the interface of fundamental and applied seed science.

For enquiries about Projects in the Leubner laboratory, please contact Prof Gerhard Leubner.

Research pages - Professor Leubner

Project pages 'The Seed Biology Place'

This project aims to investigate the interactions between bacterial endophytes and the seeds of high yielding crop species. Biopriming is a priming technology whereby seeds are hydrated and inoculated with a beneficial organism. Seed priming to modify hydration has been found to have several physiological benefits in the vegetable seed market such as increasing the uniformity and speed of germination. Biopriming however, builds upon this principal with the addition of a microbial inoculant. These are typically microorganisms that may confer benefits to the growing plant such as greater access to macro and micro-nutrients or host plant defence. This project will work with a specific nitrogen fixing bacterial endosymbiont and consider the impacts that seed inoculation with this bacteria on germination, seedling establishment and seed hormones on a range of plant species that exist in different agroecological niches. This project will utilise modern microbiological, microscopical, biochemical and hormone quantification techniques and is likely to work closely with industry partners, with the possibility of a short industry placement.

For enquiries about Projects in the Leubner laboratory, please contact Prof Gerhard Leubner.

Research pages - Professor Leubner

Project pages 'The Seed Biology Place'

Leaves are light-capturing organs, “biological solar panels”, whose “solar cells” are the subcellular organelles, chloroplasts. Chloroplast build-up is essential  for the photosynthetic production that drives our entire biosphere, and that ultimately produces our food. Chloroplasts are built primarily while meristematic cells differentiate into leaf mesophyll cells. Through mutant screens in the model plant Arabidopsis thaliana, we have identified several genes whose function is essential for chloroplast biogenesis, or whose dysfunction rescues prior defects in chloroplast development (positive elements or negative regulators of chloroplast biogenesis, respectively). In this project (several are parallel) you will focus on one of these genes, confirm its identity and examine potential mechanisms of action, through examination of molecular and cellular phenotypes of the mutants and through generation of Arabidopsis plants with elevated levels of the selected gene, or examining plants in which we have already modified the action of one of those genes in rice, one of the world’s most important crops.

Research pages - Dr Lopez

OPMD is a rare gain-of-function autosomal dominant, degenerative muscle disease that usually presents in the fifth decade of life. OPMD is due to mutations in the poly(A)-binding protein nuclear-1 (PABPN1) gene that codes for a protein that has a pivotal role in many biological pathways. We demonstrated that a gene therapy application based on silencing all endogenous PABPN1 and its replacement with normal protein can ameliorate the disease when delivered locally in the affected muscles. This approach is based on using a single viral vector that carries both the silencing and the replacement features. We are testing now different approaches where the protein inhibition is provided by destructive exon skipping where antisense therapeutics are designed to send out of frame the transcript and then produce a non-functional mRNA. This is expected to generate a safer, controllable approach that may allow the systemic treatment of the disease. It is also important to test treatments that could provide additive or synergistic effects to a gene therapy application. One of the features of OPMD is muscle atrophy, so we are testing strategies to increase muscle size and improve muscle strength.

In all of my projects, students have the opportunity to learn several techniques that are widely used in laboratories engaged in biomedical research, including: in vitro cell culture, molecular biology (e.g. Western blot, RT-PCR and quantitative PCR), histology (cryosectioning, stainings, immunofluorescence) and microscopy.

Research pages – Dr Alberto Malerba

We recently studied a very poorly characterized ribosome protein named Ribosomal protein L3-like (RPL3L), and we observed that its downregulation, obtained by delivering short harping RNA (shRNA) designed to target specifically RPL3L transcript, significantly increases muscle force in models of muscular dystrophy and muscle damage. We are now combining RPL3L downregulation with clinically relevant genetic strategies that we have developed in the laboratory, to counteract Duchenne muscular dystrophy (DMD) and Facioscapulohumeral muscular dystrophy (FSHD) in order to improve their functional efficacy.

In all of my projects, students have the opportunity to learn several techniques that are widely used in laboratories engaged in biomedical research, including: in vitro cell culture, molecular biology (e.g. Western blot, RT-PCR and quantitative PCR), histology (cryosectioning, stainings, immunofluorescence) and microscopy.

Research pages – Dr Alberto Malerba

Bacterial biofilms are a common cause of infection in surgical implants, and pin tract infection is the major complication of external fixation of fractures. Furthermore, biofilm-focused infections are phenotypically resistant to antibiotic therapy. In this microbiological project, run in collaboration with Dr Shobana Dissanayeke (Royal Holloway) and Mr Arshad Khaleel (St Peter’s Hospital, Chertsey), you will use a bioreactor to grow bacterial biofilms on orthopaedic pins and study their response to antibiotic treatments. Guided by recent results from our laboratory¹ you will investigate the social aspects of genotypic antibiotic resistance in multi-strain biofilms, extending this work by the addition of clinically relevant b-lactamase inhibitors. Our long-term objective is to inform surgical practice and reduce pin tract infection rates.

Reference: Amanatidou, E.; Raymond, B., Biofilms facilitate cheating and social exploitation of β-lactam resistance in Escherichia coli. npj Biofilms and Microbiomes 2019, 5, 36-36.

Research pages - Dr James McEvoy

Research in my group addresses one of the fundamental questions in evolutionary ecology: what are the ecological and evolutionary processes that generate, maintain, and constrain/threaten biological diversity? Using integrative and highly collaborative approaches, we try to answer the questions of (i) how and why organisms diversify phenotypically, (ii) what ecological and evolutionary forces shape reproductive barriers important in facilitating an initial reduction in gene flow between diverging populations, and (iii) what role human-induced environmental change has on biodiversity in general, and the stability of population differentiation among diverging populations in particular. Our main study system, currently, are livebearing fishes of the family Poeciliidae. Here, we work on invasive populations with a focus on trying to identify the mechanisms that facilitate invasion success. We also work on fish diversification along environmental gradients (including temperature, salinity, oxygen availability or resource availability gradients), and this includes work on fish from extreme environments (e.g., gradients of toxicity and pollution). There are always on-going and potential research projects available to MSc students in my lab, so for further information please contact me (rudiger.riesch@rhul.ac.uk).

References:

Gomes Silva G, E Cyubahiro, T Wronski, R Riesch, A Apio & M Plath (2020) Water pollution affects fish community structure and alters evolutionary trajectories of invasive guppies (Poecilia reticulata). Science of the Total Environment 730: 138912

Santi F, R Riesch, J Baier, M Grote, S Hornung, H Jüngling, M Plath & J Jourdan (2020) A century later: adaptive plasticity and rapid evolution contribute to geographic variation in invasive mosquitofish. Science of the Total Environment 726: 137908

Riesch R, RA Martin & RB Langerhans (2020) Multivariate character suites across multifarious environments: integrated responses of morphology and life history in Bahamas mosquitofish. Oikos 129(4): 480-492

Gao J, F Santi, L Zhou, X Wang, R Riesch & M Plath (2019) Geographical and temporal variation of multiple paternity in invasive mosquitofish (Gambusia holbrooki, Gambusia affinis). Molecular Ecology 28(24): 5315-5329

Research pages - Dr Riesch

You will be based in a group headed by a clinical academic.

Stroke is the third commonest cause of death in the UK. WHO estimates that by 2050 around 80% of all stroke will be in India and China. Our group has amassed the largest database of South Asian stroke in the world. We have data from UK, India and the Middle East.

It is expected that these projects will lead to publications in major international peer review journals.

This project will allow students to analyse this extensive database to search for interactions between stroke and established risk factors

Research pages - Professor Sharma

You will be based in a group headed by a clinical academic.

Stroke is the third commonest cause of death in the UK. WHO estimates that by 2050 around 80% of all stroke will be in India and China. Our group has amassed the largest database of South Asian stroke in the world. We have data from UK, India and the Middle East.

It is expected that these projects will lead to publications in major international peer review journals.

This project will allow students to analyse this extensive database to search for novel risk factors in South Asians and compare and contrast such factors with stroke in Caucasians.

Research pages - Professor Sharma

You will be based in a group headed by a clinical academic and be supervised by two clinicians.

The 5-a-day campaign was launched by the UK Government to ensure that the population eats at least five fruit and vegetables per day. Research suggests that those that do this have a lower risk of cardiovascular disease.

However, the evidence is that most people do not remember how many of their 5-a-day they have eaten. We propose to develop a new colour based flag strategy for each meal to replace the 5-a-day slogan.

This work potentially has large and important clinical and public health implications.

Research pages - Professor Sharma

Artificial intelligence is permeating all aspects of our lives and societies, and their potential to change the way in which we live is almost limitless. In this project we aim to explore the public's perceptions of artificial intelligence (AI) in science. As AI increasingly plays a significant role in various medical and scientific disciplines, understanding how the general population perceives its integration and impact is crucial.
The study will employ a range of methods focused around surveys distributed to a diverse sample population to provide statistical analysis and identify broader trends, to gather comprehensive insights into how people perceive the efficacy and ethical considerations of applying AI. Some of the key areas to be explored are:
Trust and Confidence: Investigating the level of trust the public has in AI-driven medical diagnosis and scientific outcomes.
Perceived Benefits: Assessing the perceived benefits of AI including enhanced efficiency, and accuracy of results.
Ethical Considerations: Examining ethical concerns related to AI implementation in scientific research and clinical medicine, including data privacy, bias, and accountability.
The research findings will provide valuable insights for scientists, policymakers, and educators to develop strategies for engaging with the public about AI in science and medicine effectively. By addressing concerns, promoting transparency, and highlighting the benefits, this research aims to bridge the gap between scientific advancements powered by AI and public understanding and acceptance, ultimately fostering a more inclusive and informed society.

Research pages – Dr Stuart Snowden

Metabolomics has played a significant role in bridging the gap between genotype and phenotype. Whilst metabolic architecture (i.e. the order of reactions in a metabolic pathway) is well known and highly conserved even between disparate phenotypes, metabolism is highly dynamic and it is the flow of substrate through metabolic pathways that is responsible for determining metabolic function. Therefore, simply knowing the relative metabolite composition of two groups is insufficient to provide a detailed understanding of metabolism for example, higher abundance of a given metabolite could be the result of increased production or reduced breakdown with the two causes having very different biological implications.
Fluxomics approaches provide a dynamic readout of metabolic activity by introducing an isotopically labelled substrate into a system and mapping the ‘diffusion’ of isotopic label through the metabolic network. Traditionally, these approaches have used 13C-labelled glucose however this is expensive limiting its utility, in this project we will use this in conjunction with deuterium oxide to comprehensively map functional metabolism to identify novel targets for therapeutic intervention in C9orf72 drosophila melanogaster which is a common genetic cause of frontotemporal dementia (FTD) and Amyotrophic lateral sclerosis (ALS). This project will provide training in fly handling, microscopy, mass spectrometry and advanced data analysis.

Research pages – Dr Stuart Snowden

Malnutrition is often synonymous with severe under nutrition, however, the term encompasses any instance where poor diet negatively impacts health. Whilst usually considered to be a problem exclusive to the developing world, there is growing evidence that malnutrition is also a major public health problem in wealthy nations, with individuals consuming sufficient calories but insufficient vitamins to efficiently grow, function and fight disease.
Traditionally seen as an acute problem, there is growing acceptance that exposure to malnutrition in early life (pre 5 years of age) not only impacts the individual at the time of exposure but will negatively affect their health for the rest of their life. Poor nutrition has been shown to significantly affect metabolism with shifts in metabolic pathways involved in energy metabolism as well as both anabolism and catabolism being reported. However, to date there has been no work looking at the severity of early life malnutrition required to trigger metabolic reprogramming, and negatively affect whole life health.
The aim of this project is to explore the relationship between metabolism, early life malnutrition and whole life health. We will do this using drosophila models to determine how different forms of malnutrition, including undernutrition, overnutrition and specific vitamin insufficiencies effect life expectancy, mobility and cognition and subsequently identify the metabolic anomalies that drive these changes.

Research pages – Dr Stuart Snowden

Staphylococcal Protein A (Protein A or "SPA") is a 42 kDa virulence factor produced by Staphylococcus aureus in its cell wall. SPA is well known for its ability to bind IgG molecules with very high affinity. It is widely used in biotechnology applications, such as antibody capture, immobilisation or purification to name just a few. SPA has been used widely in Life Sciences, but it has a few serious limitations. SPA recognises and binds IgGs of many different isotopes, but not all. For example native SPA does not recognise or binds human IgG3 and a few other IgGs. This severely limits its application range. This project aims to engineer SPA analogues capable of binding human IgG3. This research has huge commercial implications.

MSc projects are offered in the areas of protein engineering, molecular biomarkers of cancer, and nanoparticles and their applications. Applicants are invited to contact the supervisor, to discuss their research interests and project preferences.

Research pages – Dr Soloviev

This project aims to address critical research gaps in the detection and treatment of cancer and will aid the development of molecular screening approaches. The overall project aims includes the identification of novel biomarkers suitable for the early detection and stratification of cancer and markers to assist prognosis and treatment. Key objectives of this research include (1) Prediction of up- and down-regulated genes associated with different stages of cancer; (2) Identification of subsets of genes and proteins where the pattern of their expression levels could be used as molecular signature for the early stages of cancer, as score classifiers to assist prognosis, to evaluate drug resistance and to predict recurrence; (3) Developing of analytical molecular assays for quantitative detection of the selected markers extracted from physiological materials (for example but not limited to tissues, blood, urine or saliva samples). Such assays may rely on immunoassays, quantitative liquid chromatography approaches, qPCR or their combinations. Training in bioinformatics methods and relevant laboratory techniques will be provided.

MSc projects are offered in the areas of protein engineering, molecular biomarkers of cancer, and nanoparticles and their applications. Applicants are invited to contact the supervisor, to discuss their research interests and project preferences.

Research pages – Dr Soloviev

Members of the Bacillus genus, particularly the "Bacillus subtilis group", are known to produce amphipathic lipopeptides with biosurfactant activity. This includes the Surfactin, Fengycin and Iturin peptides that have been associated with antibacterial, antifungal, and anti-viral properties. These peptides can form micelles (small self-assembled complexes of just a few nanometres in diameter) that might affect bioavailability of these peptides. This project aims to investigate if such micelles could be used for encapsulating molecular therapeutics, and how such micelles are affected by primary bile acids synthesised in human liver, and by secondary bile acids that are formed in human intestine by intestinal bacteria. Training in relevant analytical laboratory techniques will be provided.

MSc projects are offered in the areas of protein engineering, molecular biomarkers of cancer, and nanoparticles and their applications. Applicants are invited to contact the supervisor, to discuss their research interests and project preferences.

Research pages – Dr Soloviev

Proteins are responsible for a vast range of biological functions. The ability to modify proteins in a rational manner yielded advanced therapeutics which top the list of the most commercially successful medicines (1). Yet we are only beginning to learn how to exploit the directed protein evolution (2) and how to engineer proteins or other biopolymers with the pre-determined structure or functions. One of the most interesting yet least developed areas of protein engineering research concerns the development of stimuli-sensitive molecules for therapeutic, biotechnology and materials applications. The key aim of this research PhD project is to create molecular systems capable of changing their physical or molecular properties in response to external stimuli such as ultrasound, thermal, mechanical, chemical or direct electric stimulation. In particular, we aim to develop and test thermo-responsive proteins capable of self-assembly in a sequence-specific manner and controllable disassembly in response to thermal stimuli. Another two systems under development are pH and voltage sensitive proteins. For example, we utilise self-assembling neuronal SNARE proteins as a template to devise novel stimuli-responsive proteins with tuneable sensitivity to environmental stimuli. Alternatively, the sensitivity is added to functional proteins by combining them with magnetic or elastic nanoparticles, by adding light-excitable or chemically-modifiable groups and their combinations to yield highly tuneable stimuli-responsive composite biomaterials suitable for a variety of life science and therapeutic applications.

MSc projects are offered in the areas of protein engineering, molecular biomarkers of cancer, and nanoparticles and their applications. Applicants are invited to contact the supervisor, to discuss their research interests and project preferences.

Research pages – Dr Soloviev

In nature, electrically sensitive proteins are represented largely by voltage-gated ion channels that are abundant in excitable tissues. These are transmembrane proteins responsible for maintaining ion and electric gradients and for generating action potential across cellular membranes. However, without electrically insulating membranes no electric gradients are feasible inside or outside cells, and no voltage sensitivity is required of soluble proteins that do not span cellular membranes. One area where the effect of AC/DC electric fields has been studied extensively is cell permeabilization, electroporation, biomass sterilisation and drug delivery. The mechanism mediating the effect of AC electric field is believed to involve cell membrane rupture or increased permeability due to electroporation or depolarisation of cellular membranes mediated by aberrant gating of voltage-sensitive ion channels. But some observed effects remain unexplained.   This project aims to investigate the effect of DC and AC electric stimulation on a range of model proteins. The ability of molecules to sense AC/DC electric field in solution rather than across biological membranes might provide new explanations to some unexplained biological phenomena and would allow a plethora of biotechnology applications, including the creation of biomolecular electronics and computer interfaces with biological matter.   Training in relevant instrumental analysis techniques will be provided.

Recent publications by postgraduate students in the group are listed on the research pages.

Research pages – Dr Soloviev

Genomic imprinting refers to the silencing of genes according to their parental origin (either paternally silenced and maternally expressed or vice versa). In this research I am interested in elaborating mathematical models that explore why would natural selection favour losing the advantages of diploidy to produce a functionally haploid locus

Research pages - Dr Ubeda 

Meiotic drive refers to the preferential transmission of an allele (driving allele) during meiosis in diploid individuals. In this research I am interested in elaborating mathematical models that explore why is fair (Mendelian) segregation the rule and not the exception

Research pages - Dr Ubeda 

Melanoma, in common with all solid tumours, displays excessive numbers of centrosomes, which help form the mitotic spindle. Such supernumerary centrosomes are thought to drive carcinogenesis by contributing to aneuploidy and chromosomal instability. However, much remains to be understood about the origin and the contribution of excessive centrosomes in tumorigenesis. This Masters project will continue published work (by our laboratory, doi: 10.1016/j.jid.2020.01.024) on how centrosomes and cilia are affected in melanoma. The mechanisms underlying these changes will be investigated with the aim of developing better diagnostics and treatments. A combination of cell biology, immunocytochemistry, epifluorescence microscopy and protein analysis such as Western blotting will be used in this project.

Research pages - Dr Wilkinson

Cilia are hair-like structures on the surface of many animal cells. Cilium malfunction is linked to autosomal dominant polycystic kidney disease (ADPKD), which affects 1 in 1,000 of the population, as the cilium houses polycystin-1 whose gene is frequently mutated in ADPKD. This project will investigate the role of a novel protein that interacts with polycystin-1, in collaboration with Dr Richard Sandford at University of Cambridge. A variety of cell biology and embryological techniques will be used to investigate its function using cultured fish cells and zebrafish embryos.

Research pages - Dr Wilkinson

Polyketide synthases are a class of enzymes that produce many of the antibiotics and other drugs used clinically today. Most polyketides are sourced from soil bacteria and fungi. They are also found in plants but have not been found in animals until now. We recently published a paper (https://doi.org/10.1016/j.mod.2019.04.001) showing for the first time that one such enzyme is present in fish. Although we studied the zebrafish enzyme, homologues are present in other fish as well as reptiles, birds and some mammals. What chemical is produced by this enzyme is unknown. This project will discover the product of this enzyme and test if it has antibacterial effects or other pharmaceutical activities. A combination of protein expression in cultured fish or mammalian cells or yeast or E. coli, followed by bioassays will be used in this project.

Research pages - Dr Wilkinson

A hallmark of Parkinson’s disease is the presence of large aggregates of protein called Lewy Bodies in affected neurons. In collaboration with colleagues at the University of Cambridge, we have recently published a paper (doi: 10.1242/bio.054338) that shows that related, possibly precursor, structures called aggresomes prevent the centrosome and cilia from functioning. The centrosome is the microtubule organising centre of the cell and contributes to the internal organisation of the cell and intracellular transport. Loss of these functions could lead to neuronal disease. Notably, cilia are involved in olfaction, the sense of smell, which is lost in Parkinson’s disease, and the presence of aggresomes prevents cilia from forming. This project will investigate the mechanisms by which the aggresome affects these other two organelles. A combination of cell biology, immunocytochemistry, epifluorescence microscopy and zebrafish genetics will be used in this project.

Research pages - Dr Wilkinson

Early ear development in fish involves the formation of otoliths, protein-calcium calcium carbonate complexes whose generation and anchoring both involve the action of cilia. They are related to the structures in the human ear used in the sense of balance. We recently published, in collaboration with Ken Kramer and colleagues at Creighton University in the USA, a paper (doi: 10.1016/j.mod.2019.04.001) showing that a novel type of enzyme is involved in formation of these structures. This project will investigate the mechanism by which this enzyme contributes to otolith formation. A combination of zebrafish genetics, embryology and tissue expression techniques will be used in this project.

Research pages - Dr Wilkinson

In many cancers the primary cilium that is present on healthy cells is lost. This may contribute to cancer development by disturbing the reception of the signals a cell receives that regulate cell division. Furthermore, cilia are incompatible with cell division, which is inappropriately and excessively occurring in cancer, as the component centrioles are required to form the poles of the mitotic spindle. In 2017 we published a paper (doi: 10.1242/jcs.196642) showing that a centrosome satellite protein called BCAP was a novel inhibitor of ciliogenesis. This project will test if inhibiting or removing BCAP from cells can prevent cell division and therefore be a potential anti-cancer drug target. A combination of cell biology, immunocytochemistry, epifluorescence microscopy and protein analysis such as Western blotting will be used in this project.

Research pages - Dr Wilkinson

Research into improving our understanding of disease treatments is often focused on the characterisation cell signalling regulation caused by current or new medicines or bioactive natural products. Rodents are traditionally used as models for these studies, in addition to human or mammalian cell lines. The models are often difficult to manipulate, and can be associated with ethical considerations. Our laboratory specialises in these studies using an innovative model system, the social amoeba Dictyostelium discoideum. This system allows the rapid manipulation of cells, including CRISPR knockout approaches and expression of fluorescently tagged proteins in isogenic cell line enabling biochemical assays, to discover the molecular and cellular effects and mechanisms of action of medicines or health/disease related natural products (e.g. Warren et al 2020 PNAS; Perry et al 2019 BJP; Sharma et al 2019 Autophagy). We used Dictyostelium to modelled the effects of compounds relating to a range of diseases include various cancer types, multiple epilepsies, Alzheimer’s disease, bipolar disorder, infection and polycystic kidney disease and others. We also often works with industry, focusing on wide-ranging compounds including various cannabinoids, medium chain fatty acid related to ketogenic diets, naturally occurring antibiotics, flavonoids, and traditional (herbal) remedies from around the world.

A Maters student joining our laboratory will learn a wide variety of key skills used widely in molecular cell biology and modelling, to equip them for ongoing academic studies or to move into an industry setting. We are fully equipped for research with bespoke facilities for tissue culture, microscopy and molecular biology studies. 

We would be delighted to hear from high-achieving students with some background and interest in molecular cell biology, who are keen to developing their careers in a scientific setting.

Research Pages - Professor Williams

Our laboratory (http://AGCTlab.org) works on the development of new gene and stem cell therapies for rare and common diseases. Recently we have been working on novel therapeutic strategies for spinal cord injury, spinal muscular atrophy and ataxia telangiectasia (A-T). The latter is a rare disease characterised by progressive degeneration in cerebellum, high risk of cancer and immunodeficiency. It is caused by defects in the gene known as ataxia telangiectasia mutated (ATM). The most advanced gene therapy technology, “genome editing”, can be used to introduce specific changes in the DNA, including the repair of a faulty gene: this could be applied as a therapy for A-T. Genome editing has undergone a revolution over the last few years with the introduction of a system called CRISPR, which has greatly facilitated the process. For this research project we will use the CRISPR system to test several ways to repair the faulty gene in A-T. We will initially work with easy-to-grow human cells in the lab, and eventually the most effective A-T gene repair strategies will be tested in human blood stem cells. If our proposed studies are successful, follow-up projects would explore these novel gene repair methods in blood stem cells from people affected by A-T. We will also study possible side effects of these gene repair methods. If successful, this work could eventually pave the way for the treatment of blood disease in A-T.

Research pages - Professor Yanez