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ICGEB Research Grants awarded under the 2019 Call for applications
Title: Ferroptosis-like cell death in plants
Principal Investigator: Dr. Gabriela Pagnussat, Instituto de Investigaciones Biologicas – CONICET, Universidad Nacional de Mar del Plata,
Argentina
ICGEB Reference No. CRP/ARG19-06
Abstract: Plants are continually exposed to various environmental stresses. As they are unable to escape, tolerance to
changing conditions is critical for plant growth and survival. In this context, regulated cell death plays a critical
role for specific responses to both abiotic and biotic stresses. We recently discovered that a process similar to the
iron-dependent cell death pathway, named ferroptosis, which was first observed in tumour cells, takes place in
plants in response to heat stress. Notably, if ferroptosis is prevented by using canonical inhibitors, plants can
endure otherwise lethal conditions. Although we found that there are some morphological and biochemical
features conserved between animal and plant ferroptosis, plant cells have particular characteristics and
responses, so the molecular mechanisms underlying this process in plants are still unknown. In this project we
aim to study such mechanisms using biochemical, genomic and molecular tools. As suppressing ferroptosis
allows plants to cope with high temperatures, these studies open a new alternative for researchers to study
innovative biotechnological approaches for crop protection during times of extreme temperature fluctuations,
which are increasingly likely to affect diverse plant species as a result of climate change.
Title: Engineering pro-vitamin A rich orange eggplant: Potential to reduce vitamin A deficiency in developing
countries
Principal Investigator: Dr. Abdun Noor Muhammad Iftekhar Alam, National Institute of Biotechnology, Dhaka, Bangladesh
ICGEB Reference No. CRP/BGD19-02
Abstract: Vitamin A deficiency (VAD) has been one of the world’s major human health problems for a long time. Among
various approaches, fortification of major food crops with pro-vitamin A (carotene) is considered the most
feasible solution. Eggplant is a vegetable consumed in significant quantities in regions where VAD is highly
prevalent. Thus, we propose the development of carotene-fortified eggplant through genetic engineering. We
will express two rate-limiting enzymes, phytoene synthase (Psy) and phytoenedesaturase (CrtI), through genetic
transformation. The genetically modified eggplant is expected to produce high amounts of carotene in the
fruits. We will also verify the amount of bio-available pro-vitamin A in various cooked dishes made from the
transgenic plants. Successful bioengineering of eggplant would have the potential to combat VAD in
developing countries.
Title: Mining the soybean leaf microbiome for disease-suppressive microbes
Principal Investigator: Dr. Paulo JosĂ© Pereira Lima Teixeira, Department of Biology, “Luiz de Queiroz” College of Agriculture (ESALQ)
University of SĂŁo Paulo, Piracicaba, Brazil
ICGEB Reference No. CRP/BRA19-05_EC
Abstract: Soybean is the most important crop in Brazil and exportation of this commodity is a driving force of Brazilian
agriculture and economy. Asian Soybean Rust (ASR), however, severely threatens soybean production in Brazil.
There are no commercially available cultivars that are fully resistant to ASR and this disease is mainly controlled
through routine applications of fungicides, which is a costly practice with potential environmental impacts. In
recent years, it has become evident that plants establish intimate relationships with commensal microbes that
form complex microbiomes on or within them. In this project, we will define the composition of bacterial
communities colonising soybean leaves, to understand how ASR affects the plant microbiome. We will also
assemble a collection of soybean-associated bacteria to search for strains that can prevent the establishment of
ASR. This effort may support the development of effective biofungicides against one of the most important
plant diseases in Brazil.
Title: Low cost and variability-tolerant cell-free biosensors for RNA viruses
Principal Investigator: Dr. Fernan Federici, Pontificia Universidad Catolica de Chile, Santiago, Chile
ICGEB Reference No. CRP/CHL19-01
Abstract: We propose the development of ratiometric cell-free toehold sensors (CFTSs) in low cost E. coli TX-TL crude cell
extracts for the detection of RNA viruses. Ratiometric CFTSs will be tolerant to variability, delivering more robust
readouts. This challenge will be addressed by: (i) implementing CFTSs in self-manufactured
transcription/translation (TX-TL) cell extracts that are optimised for RNA & DNA stability and for the use of low
cost energy regeneration reagents; (ii) studying, identifying and correcting the sources of variability in TX-TL cell-
free reactions through mathematical modelling and Ratiometric Dual Analysis; and (iii) engineering novel Tx-TL-
based Ratiometric CFTSs for the detection of PVY RNA virus, as a proof-of- concept. Implementing CFTSs in self-
manufactured cell extracts would allow cheaper design-build-test cycles for prototyping sensors in developing
countries. We expect this project to develop foundational knowledge on CFTS engineering, as well as enhancing
local capacity and advanced resources for cell-free synthetic biology.
Title: Structural and functional study of Hepatitis A Virus 2C protein and its role in virus replication
Principal Investigator: Dr. Sheng Cui, Institute of Pathogen Biology, Chinese Academy of Medical Science, Beijing, China
ICGEB Reference No. CRP/CHN19-02
Abstract: Hepatitis A virus (HAV) spreads via contaminated foods, causing millions of cases of hepatitis infection. HAV
outbreaks can erupt explosively and lead to devastating consequences. Despite the availability of an effective
prophylactic vaccine, HAV still contributes to mortality, largely because there is no effective drug.. HAV belongs
to the Picornaviridae, and although the structure of the HAV capsid has been solved, it provides limited insights
into the replication of HAV, and the role of the nonstructural protein in replication remains enigmatic. In this
research proposal, we focus on HAV 2C protein: 2C plays a central role in virus replication and participates in
almost every aspect of the virus life-cycle, hence it is a potentially important drug target. In this project, we aim
at: (i) investigating the functions of HAV 2C; (ii) determining its high-resolution structure; and (iii) validating the
structural findings via mutagenesis. Knowing the structure of HAV 2C will allow virtual screening for drug leads,
and should eventually assist in the development of antiviral drugs.
Title: Uncovering developmental and transcriptional mechanisms of the early synthesis of cytotoxic, antimicrobial,
and cardiotonic bufadienolides in toads
Principal Investigator: Dr. Jennifer Lynn Stynoski, Clodomiro Picado Institute, University of Costa Rica, San José, Costa Rica
ICGEB Reference No. CRP/CRI19-04_EC
Abstract: A class of steroids called bufadienolides have shown enormous potential as natural products to treat and
diagnose cancer, microbial and fungal infections, preeclampsia, and heart disease..Bufadienolides are
synthesised in the glands of toads as chemical defences against predators and pathogens, and have long been
delivered in crude toad venom as traditional medicine, with diverse detrimental side effects. The development
of these into targeted therapeutic tools is limited by a lack in our understanding of the biosynthetic and
genomic pathways underlying the production and activities of bufadienolides in animal tissues. Using four
different Costa Rican toad species, whose bufadienolides vary in their degree of toxicity, we propose to identify:
(i) when and where bufadienolide biosynthesis starts and (ii) the changes in gene expression that are associated
with their initial biosynthesis in toads. Understanding how changes in gene expression allow toad cells to make
bufadienolides will give us the foundation necessary to research and produce specific therapeutic targets in
transgenic models in the future.
Title: Piperine for the prevention of breast cancer
Principal Investigator: Dr. Rama Ibrahim Khalaf Mahran, Department of Pharmacology, Faculty of Medicine, Suez Canal University,
Ismailia, Egypt
ICGEB Reference No. CRP/EGY19-04_EC
Abstract: Breast cancer is the first cause of cancer deaths among the North African women, including Egyptian women.
Prevention of breast cancer represents a cost-effective strategy, as an alternative to treatment. Piperine, the
spice derived from black and long pepper, has been shown to have anti-carcinogenesis effects. We question
whether piperine will effectively prevent breast cancer by targeting human dysplastic breast stem cells. The aims
of this project are: (i) to evaluate the preventive efficacy of piperine against breast cancer in human cell line-
derived mammary organoids; (ii) to learn how to establish primary human normal, dysplastic, and cancer 3D
mammary organoid cultures; and (iii) to grow primary organoids in cultures in Egypt. Mammary organoids will
be treated with piperine and the effects of piperine on stem cell self-renewal, stemness, viability, growth and
proliferation, and differentiation will be tested. Finally, the molecular pathways by which piperine targets
dysplastic stem cells will be identified.
Title: Comparative lipidomics for development of Mycobacterium tuberculosis-based lipid biomarkers
Principal Investigator: Dr. Feven Tigistu-Sahle, Ethiopian Biotechnology Institute, Addis Ababa, Ethiopia
ICGEB Reference No. CRP/ETH19-05_EC
Abstract: Mycobacterium tuberculosis (Mtb) is the causative agent for Tuberculosis (TB), a leading cause of death globally. A
quarter of the global population is estimated to be latently infected with Mtb, meaning that their immune
system can effectively contain this infection, to remain healthy. Of these latently infected individuals, fewer than
10% progress to active TB infection during their lifetime. Very little is known about the factors that determine
these risks and there is lack of effective biological markers to differentiate the latent from active infections.
Several studies have established the role of lipids in Mtb survival within the host environment and during its
progression to the active state. This project aims to use modern analytical methods to compare the lipid profiles
of Mtb at different stages of infection, to identify novel lipid molecules for use as biomarkers. The discovery of
reliable biomarkers will advance treatment options through the rapid and accurate identification and
differentiation of individuals with latent and active Mtb infections.
Title: Examination of the interaction between Candida and oral squamous cell carcinoma cells on the level of
extracellular vesicles
Principal Investigator: Prof. Attila GĂĄcser, Department of Microbiology, University of Szeged, Hungary
ICGEB Reference No. CRP/HUN19-01
Abstract: According to our previous findings, oral squamous cell carcinoma (OSCC) patients are characterised by having
increased yeast abundance in their oral cavity, compared with healthy individuals. Therefore, in this project we
aim to explore the nature of an possible interaction, between local yeasts, (represented by Candida species) and
oral tumour cells in vitro. Our purpose is to investigate yeast-tumour cell interaction at the level of extracellular
vesicles (EVs), as EVs have recently been reported to be major mediators of intercellular (and inter-kingdom)
communications. In this project, we also aim to thoroughly examine the physical interaction between tumour
exosomes and Candida cells, as well as examining the effect of Candida EVs on OSCC cells. We plan to use OMICs
analyses, biochemical assays, flow cytometry and microscopy experiments to better understand the molecular
bases of the potential information transmission between fungal and cancer cells at the level of extracellular
vesicles.
Title: A molecular and immunological investigation of leishmaniasis from unusual foci of cutaneous and visceral
disease in India and Nepal
Principal Investigator: Dr. Manju Jain, Central University of Punjab, Bathinda, India
ICGEB Reference No. CRP/IND19-01
Abstract: Leishmaniasis is caused by transmission of the Leishmania parasite through the bite of infected sandflies, which
results in Cutaneous Leishmaniasis (CL), causing skin lesions, and Visceral Leishmaniasis (VL), a deadly systemic
disease. The different clinical outcomes result from the interplay between the infecting Leishmania species and
the host's immune status. Recently, the disease has spread to newer areas, where it shows atypical
characteristics: such that the Leishmania donovani species, which typically causes visceral disease (VL), now
causes cutaneous disease (CL). We propose to study two, newly-emerging, atypical foci of leishmaniasis - one in
Himachal Pradesh, India, and the other in the western Hilly and Terai regions of Nepal - to understand why L.
donovani has changed from being a deadly VL-causing parasite to being a less dangerous CL-causing parasite.
L. donovani will be isolated from cutaneous lesions in these areas of India and Nepal, and genome sequencing
will be performed to identify gene variants that may be associated with atypical cutaneous disease.
Immunological correlates in VL and CL patients will also be investigated.
Title: Determination of signal flow in cellular systems using the yeast fat regulating network as a model
Principal Investigator: Dr. Bader F. Al-Anzi, Kuwait Institute for Scientific Research, Safat, Kuwait
ICGEB Reference No. CRP/KWT19-01
Abstract: We have used genetic, proteomic and physiological methods to characterise a protein network that regulates fat
storage in yeast. In this network, the contribution of a given structure to its overall signalling output can be
determined by simply measuring fat in cells missing that structure. Thus, it can provide empirical parameters to
computationally model signal flow within a cellular network. We have succeeded in showing that the
importance of each protein to network output is dependent on a topological parameter called Katz centrality.
However, it is also important to establish the amount of signalling carried by individual protein connections. To
rephrase what we are attempting to do: if these connections are highways, how much traffic are they carrying?
This goal will be achieved by following a multidisciplinary approach utilising Mass Spectrometry, yeast strains
that cannot form a given protein connection, a variety of metabolic assays, and computational analysis. The
acquired data will be used to build a predictive signal flow model.
Title: CRISPRi genetic screen in identifying surfaceome addiction in glioblastoma multiforme
Principal Investigator: Dr. Mohamad Aimanuddin Mohtar, UKM Medical Molecular Biology Institute (UMBI), UKM Medial Centre, Kuala
Lumpur, Malaysia
ICGEB Reference No. CRP/MYS19-04_EC
Abstract: Glioblastoma Multiforme (GBM) is the deadliest disease of the central nervous system. GBM-diagnosed patients
have a low survival rate, averaging 12-15 months’ life expectancy. Current standard-of-care therapies have
provided poor efficacy in treating GBM. Our analysis, utilising the public genomics database, revealed that many
genes encoding the cell surface proteins (termed surfaceome) are highly expressed in GBM, suggesting their
importance in GBM pathogenesis. Thus, the general aim of this study is to identify novel oncogenic drivers
within the cell surface sub-proteome that support GBM growth and progression. This will be achieved via the
utilisation of a CRISPRi genetic screen targeting the most significantly upregulated components of the GBM
surfaceome. The candidate hits from the screen will be functionally validated using cell-based and mouse model
experimental assays. This study will facilitate the discovery of novel oncogene addictions in GBM that could
potentially be targeted in the clinic, either individually or as part of a combination therapy.
Title: Paleogenomic characterisation of human pathogens spanning the Native-European contact in Latin America
Principal Investigator: Dr. María C. Ávila Arcos, International Laboratory for Human Genome Research, National Autonomous University
of Mexico, Querétaro, México
ICGEB Reference No. CRP/MEX19-03
Abstract: Understanding the genetic makeup of pathogens involved in major pandemics is crucial for informing strategies
to face the potential devastating effects of a reintroduction. Ancient DNA studies have revealed the causes of
major epidemics and the genetic makeup of some ancient human pathogens. This is of interest in places like
Mexico and Argentina, where a large fraction of the Native population died as a consequence of devastating
outbreaks caused by pathogens introduced during European colonisation, some of which still pose
epidemiological threats today.
In this project we will (i) extract ancient pathogen DNA from archaeological remains from Mexico and
Argentinian Patagonia to reveal the extent of pathogen diversity present in each region, before and after
European colonisation; (ii) reconstruct whole genomes and resolve their phylogenetic relationship to other
strains to unveil the evolutionary patterns of endemic versus introduced infectious diseases; (iii) identify
genomic changes associated woth pathogenicity and host-pathogen interactions in the ancient strains.
Title: Next generation diagnostics and characterisation for emerging viruses and virus-like agents of pome and stone
fruits in Montenegro
Principal Investigator: Dr. Jelena Zindovic, Biotechnical Faculty, University of Montenegro, Podgorica, Montenegro
ICGEB Reference No. CRP/MNE19-01
Abstract: New emerging viruses and virus-like pathogens, as well as new variants of existing pathogens, pose a serious
threat to agricultural production. The availability of metagenomic analyses through Next Generation
Sequencing (NGS) has made accessible whole plant and pathogen genomes, and has become a powerful tool in
the diagnosis of unknown plant diseases. The goal of this project is to acquire the knowledge, skills and
competences in using the state-of-the-art NGS technologies to detect and characterise existing and emerging
viruses and virus-like agents of pome and stone fruits, and to contribute to the development of their disease
management in Montenegro.
Title: Diagnostic, prognostic and predictive biomarkers for bladder cancer management
Principal Investigator: Prof. Zivko Popov, Research Center for Genetic Engineering and Biotechnology “Gorgi D. Efremov”, Academy of
Science and Arts of the Republic of North Macedonia (MASA), Skopje, North Macedonia
ICGEB Reference No. CRP/MKD19-02
Abstract: Bladder cancer (BC) is one of the most common types of cancer worldwide, and molecular defects associated
with the initiation of the carcinogenic process in this type of tumour has great clinical importance. Different
molecular changes have been found in the tissue samples of patients with BC, which could be used as markers
for non-invasive early diagnosis, as well as being potential prognostic and/or predictive biomarkers for patient
management.
The main aim of this project is the determination of the molecular (DNA, RNA, protein) changes in the early
stages of the disease, present in the tissue and/or blood or urine of patients with bladder cancer. The potential
use of the observed molecular changes as diagnostic, prognostic and predictive markers for clinical
management of this disease will also be evaluated.
Title: Design and test of in vitro and in vivo applicators for the use of electromagnetic energy against the Malaria
parasite
Principal Investigator: Dr. Lorena Michelle Coronado, INDICASAT AIP, Panama City, Panama
ICGEB Reference No. CRP/PAN19-01
Abstract: Or group has successfully develped the use of microwave non-thermal irradiation in in vitro tests as a potentially
effective malaria treatment, acting by inhibiting the growth of the causative parasite, P. falciparum..We are now
at the challenging point when it is necessary to design and build applicators for the delivery of this energy in an
effective and safe way in vivo. To achieve this task it is necessary to study the dynamics of blood movement
using a fluid moving setup that simulates real blood circulation, with the application of microwaves at a given
point of the circulating system. When the right parameters to achieve killing are achieved, tests will be carried
out on mice infected with malaria.
Our objective is to design, build and optimise applicators for the treatment of malaria using electromagnetic
energy. The aims of this project are: (i) to design and test an applicator to be used against P. falciparum, based
on parallel plates; (ii) to design and test an applicator to be used against P. falciparum, based on constant fluid;
and (iii) to test the applicators against malaria in an in vivo model.
Title: Are prion (PrP) and MARCKS proteins functional partners in vivo? MARCKS proteins as potential components of
prion and Alzheimer’s neurodegenerative pathways
Principal Investigator: Prof. Edward MĂĄlaga-Trillo, Universidad Peruana Cayetano Heredia, Lima, Peru
ICGEB Reference No. CRP/PER19-02
Abstract: Alzheimer’s, Parkinson’s and prion diseases result from the cunning ability of toxic proteins to hijack biochemical
signals normally used by neurons to communicate. One such signalling pathway involves the modulation of cell
adhesion and neurotransmission by the prion protein (PrP) and its control over Src family kinases (SFKs). This
mechanism is only partially understood, as PrP can interact with other molecules whose involvement in
neurodegeneration remains unclear. Among these, MARCKS proteins are of special interest because, like SFKs,
they associate with neuronal cell membranes and participate in the control of cell adhesion and
neurotransmission. This proposal assesses the potential role of MARCKS proteins as, as yet unrecognised,
downstream mediators of PrP neurotoxicity, complementary to SFKs. Using a combination of genetic, cell
biological, biochemical and behavioural approaches in zebrafish embryos, we will examine the formation of
functional PrP/SFK/MARCKS complexes, their involvement in neuronal physiology and their contribution to
prion and Alzheimer’s neurodegeneration.
Title: Development of bacterial inoculants for biological control of plant pathogens
Principal Investigator: Prof. Djordje Fira, Faculty of Biology, University of Belgrade, Serbia
ICGEB Reference No. CRP/SRB19-02
Abstract: Biological control of plant pathogens has become an important alternative to the extensive use of chemical
pesticides in modern agriculture. The aim of the proposed project is to identify the best strains for the
formulation of biocontrol inoculants from the existing laboratory collection. In our previous work, we have
already characterised several strains of genus Bacillus at a genetic and biochemical level, including the basis of
their strong activities against important fungal and bacterial plant pathogens in experiments both in vivo and in
situ. Therefore, the focus of our research will be on several objectives: (i) to test the biocontrol capacity of
selected strains in greenhouse and field trials on crops most important for Serbian agriculture; (ii) to expand the
existing collection with Gram-negative bacteria, including their molecular and biochemical characterisation and
determination of anti-pathogenic activity; and (iii) metagenomic studies of plant samples during their treatment
with biocontrol agents, in order to determine the dynamics of plant microbiome and its influence on plant
growth.
Title: Regulation of intracellular complexes formed by dipeptide repeats from C9ORF72 mutation
Principal Investigator: Dr. Boris Rogelj, Faculty of Chemistry and Chemical Technology, University of Ljubljana, Slovenia
ICGEB Reference No. CRP/SVN19-03
Abstract: Progressive neuronal loss is a key feature in several forms of dementia and movement disorders. One signature
microscopic feature that can be observed post-mortem in the brains of patients diagnosed with these diseases,
is the abnormal aggregation of certain proteins. In Frontotemporal Dementia (FTD) and Amyotrophic Lateral
Sclerosis (ALS) this protein is TDP-43. The most common mutation in ALS and FTD is in the C9ORF72 gene and
leads to disease causing aggregations of TDP-43. The mutation in C9ORF72 gene results in formation of toxic
RNAs or proteins, whose direct linkage with the disease still needs to be determined. With this proposal we aim
to identify the set of proteins that interact with C9ORF72 toxic proteins in living cells, to examine whether the
interactions lead to TDP-43 aggregation and to determine how these interactions could be used to attenuate
their toxicity.
Title: ValitaCHO: Faster and cheaper manufacturing of biopharmaceuticals using next generation “super” CHO cell
lines generated using a novel directed evolution and synthetic biology strategy
Principal Investigator: Dr. Deepak Balaji Thimiri Govinda Raj, CSIR Biosciences, Pretoria, South Africa
ICGEB Reference No. CRP/ZAF19-05_EC
Abstract: The biopharmaceutical industry is rapidly growing and is crucial to the well-being of global citizens.
Biotherapeutics offer significant advantages and we now have the theoretical toolkit to treat almost all diseases.
Significant challenges exist in transferring it to a viable solution. Currently over 70% of the commercial
biotherapeutics are manufactured using Chinese Hamster Ovary (CHO) cells, but it is widely acknowledged that
in their current format this is unlikely to continue. As the complexity increases, the economics of current CHO-
based biomanufacturing further deteriorates and, as we prepare for more futuristic applications, the CHO
expression system needs to be significantly improved or to be completely replaced. The key objective of this
project is to generate "super" CHO cell lines for improved biopharmaceutical production. Herein, we describe an
approach to utilise all of the knowledge generated to date on CHO cells and to evolve this to develop a cell line
more fit for purpose, in terms of both cost and production capacity.
Title: Comparative study of Sickle Cell Disease modifiers in Ghana, Nigeria and Tanzania. Investigation of foetal
haemoglobin parameters and clinical manifestation
Principal Investigator: Dr. Siana Nkya, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania
ICGEB Reference No. CRP/TZA19-01
Abstract: Sickle Cell Disease (SCD) is an inherited blood disorder that is caused by a mutation leading to the synthesis of
abnormal haemoglobin and red blood cells (RBC). SCD is clinically characterised by insufficient blood (anaemia),
episodes of pain, painful swellings of the hands and feet, frequent infections and delayed growth. SCD patients
inherit the sickle mutation with other genetic combinations, which are known as haplotypes. Five SCD
haplotypes have been described: Senegal, Benin, Central African Republican, Cameroon, and Arab-Indian. SCD
symptoms are different among individuals with different haplotypes.
Foetal Haemoglobin (HbF) is a major modifier of the severity of SCD symptoms; however the levels and
distribution of HbF in RBCs is different among individuals with SCD and across SCD haplotypes, leading to the
observed differences in SCD symptoms.
This study will be one of the first in Africa to systematically compare HbF levels and distribution with clinical
symptoms across SCD patients from different geographical locations and with different SCD-haplotypes.
Title: The synthesis and testing of novel drugs for the treatment of Diabetes Mellitus
Principal Investigator: Dr. Varma Hemant Rambaran, The University of Trinidad and Tobago, Arima, Trinidad and Tobago
ICGEB Reference No. CRP/TTO19-01
Abstract: Present anti-diabetic medicines on the market still rely on the signalling action of insulin as a means of
remedying the hyperglycemic levels in the body. This is a major problem in the case of Type II Diabetes, where
the cells’ insulin receptors have become desensitised to the action of insulin and therefore an alternative form of
therapy is needed. Vanadyl complexes have had a successful history, as insulin mimetics, in attenuating blood
glucose levels, however, a shortcoming is the gastric disorders that are associated with oral administration. To
overcome this disadvantage,, it has been proposed that a means to avoid such deleterious effects is to optimise
or change the specie of binding ligand. The project discussed herein focuses on the synthesis and biological
evaluations of two novel vanadyl complexes, with the hope of obtaining at least one drug that will be both
pharmacologically effective and safe when used as a diabetes-therapeutic agent.
Title: CD300f immune receptors in neuroinflammation and neuroplasticity: role for behavioural alterations relevant for
major depression disorder
Principal Investigator: Dr. Hugo Peluffo, Institut Pasteur de Montevideo, Uruguay
ICGEB Reference No. CRP/URY19-01
Abstract: Depressive disorders affect more than 350 million people worldwide. Recently, increased immune responses and
higher levels of inflammatory molecules have been found in depressed patients. The immune system is our
defence system, being responsible for identifying and protecting the body against potential threats. However,
dysfunctional immune activation after stress exposure can be detrimental, and a condition called
neuroinflammation may impact the function of, and communication between, brain cells in areas responsible
for controlling behaviours, such as mood and pleasure/reward. Our goal is to study the receptors for CD300f, a
molecule present in both immune and brain cells, which is involved in the control of immune activation and in
reduction of inflammation. We will use genetically modified mice and human studies to investigate whether
CD300f receptors can control the spread of neuroinflammation, and the changes in brain cells, and resultant
behaviours relevant for depression. With this knowledge, we can propose new pharmacological strategies to
treat depression.
Title: Characterisation of a GWAS-derived QTL for yield-related traits in Vietnamese landraces suitable for local rice
breeding program
Principal Investigator: Dr. Ngan Giang Khong, Agricultural Genetics Institute, Hanoi, Vietnam
ICGEB Reference No. CRP/VNM19-03
Abstract: Panicle architecture is one of the key components of rice yield and exhibits a large diversity. To identify the
morphological and genetic determinants of panicle architecture, a genome-wide association study (GWAS)
using an original panel of Vietnamese landraces, was performed. Twenty-nine stable QTLs associated with
several panicle traits were detected over the two years. Interestingly, a new single QTL with co-location of both
Spikelet Number (SpN) and Secondary Branch Number (SBN) traits was observed (namely QTL_9), and no
functionally characterised genes were co-located in this genomic region of 780 Kb. The aim of this project is to
characterise the GWAS-derived QTL9 and the associated genes related to rice yield. The main objectives are: (i)
to characterise the QTL9 through bi-parental population; (ii) to analyse the function of candidate genes in
Vietnamese varieties by transgenic plants; and (iii) to develop the genetic markers for rice breeding programmes
in Vietnam.

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Cr ps awards_2019

  • 1. ICGEB Research Grants awarded under the 2019 Call for applications Title: Ferroptosis-like cell death in plants Principal Investigator: Dr. Gabriela Pagnussat, Instituto de Investigaciones Biologicas – CONICET, Universidad Nacional de Mar del Plata, Argentina ICGEB Reference No. CRP/ARG19-06 Abstract: Plants are continually exposed to various environmental stresses. As they are unable to escape, tolerance to changing conditions is critical for plant growth and survival. In this context, regulated cell death plays a critical role for specific responses to both abiotic and biotic stresses. We recently discovered that a process similar to the iron-dependent cell death pathway, named ferroptosis, which was first observed in tumour cells, takes place in plants in response to heat stress. Notably, if ferroptosis is prevented by using canonical inhibitors, plants can endure otherwise lethal conditions. Although we found that there are some morphological and biochemical features conserved between animal and plant ferroptosis, plant cells have particular characteristics and responses, so the molecular mechanisms underlying this process in plants are still unknown. In this project we aim to study such mechanisms using biochemical, genomic and molecular tools. As suppressing ferroptosis allows plants to cope with high temperatures, these studies open a new alternative for researchers to study innovative biotechnological approaches for crop protection during times of extreme temperature fluctuations, which are increasingly likely to affect diverse plant species as a result of climate change. Title: Engineering pro-vitamin A rich orange eggplant: Potential to reduce vitamin A deficiency in developing countries Principal Investigator: Dr. Abdun Noor Muhammad Iftekhar Alam, National Institute of Biotechnology, Dhaka, Bangladesh ICGEB Reference No. CRP/BGD19-02 Abstract: Vitamin A deficiency (VAD) has been one of the world’s major human health problems for a long time. Among various approaches, fortification of major food crops with pro-vitamin A (carotene) is considered the most feasible solution. Eggplant is a vegetable consumed in significant quantities in regions where VAD is highly prevalent. Thus, we propose the development of carotene-fortified eggplant through genetic engineering. We will express two rate-limiting enzymes, phytoene synthase (Psy) and phytoenedesaturase (CrtI), through genetic transformation. The genetically modified eggplant is expected to produce high amounts of carotene in the fruits. We will also verify the amount of bio-available pro-vitamin A in various cooked dishes made from the transgenic plants. Successful bioengineering of eggplant would have the potential to combat VAD in developing countries. Title: Mining the soybean leaf microbiome for disease-suppressive microbes Principal Investigator: Dr. Paulo JosĂ© Pereira Lima Teixeira, Department of Biology, “Luiz de Queiroz” College of Agriculture (ESALQ) University of SĂŁo Paulo, Piracicaba, Brazil ICGEB Reference No. CRP/BRA19-05_EC Abstract: Soybean is the most important crop in Brazil and exportation of this commodity is a driving force of Brazilian agriculture and economy. Asian Soybean Rust (ASR), however, severely threatens soybean production in Brazil. There are no commercially available cultivars that are fully resistant to ASR and this disease is mainly controlled through routine applications of fungicides, which is a costly practice with potential environmental impacts. In recent years, it has become evident that plants establish intimate relationships with commensal microbes that form complex microbiomes on or within them. In this project, we will define the composition of bacterial communities colonising soybean leaves, to understand how ASR affects the plant microbiome. We will also assemble a collection of soybean-associated bacteria to search for strains that can prevent the establishment of
  • 2. ASR. This effort may support the development of effective biofungicides against one of the most important plant diseases in Brazil. Title: Low cost and variability-tolerant cell-free biosensors for RNA viruses Principal Investigator: Dr. Fernan Federici, Pontificia Universidad Catolica de Chile, Santiago, Chile ICGEB Reference No. CRP/CHL19-01 Abstract: We propose the development of ratiometric cell-free toehold sensors (CFTSs) in low cost E. coli TX-TL crude cell extracts for the detection of RNA viruses. Ratiometric CFTSs will be tolerant to variability, delivering more robust readouts. This challenge will be addressed by: (i) implementing CFTSs in self-manufactured transcription/translation (TX-TL) cell extracts that are optimised for RNA & DNA stability and for the use of low cost energy regeneration reagents; (ii) studying, identifying and correcting the sources of variability in TX-TL cell- free reactions through mathematical modelling and Ratiometric Dual Analysis; and (iii) engineering novel Tx-TL- based Ratiometric CFTSs for the detection of PVY RNA virus, as a proof-of- concept. Implementing CFTSs in self- manufactured cell extracts would allow cheaper design-build-test cycles for prototyping sensors in developing countries. We expect this project to develop foundational knowledge on CFTS engineering, as well as enhancing local capacity and advanced resources for cell-free synthetic biology. Title: Structural and functional study of Hepatitis A Virus 2C protein and its role in virus replication Principal Investigator: Dr. Sheng Cui, Institute of Pathogen Biology, Chinese Academy of Medical Science, Beijing, China ICGEB Reference No. CRP/CHN19-02 Abstract: Hepatitis A virus (HAV) spreads via contaminated foods, causing millions of cases of hepatitis infection. HAV outbreaks can erupt explosively and lead to devastating consequences. Despite the availability of an effective prophylactic vaccine, HAV still contributes to mortality, largely because there is no effective drug.. HAV belongs to the Picornaviridae, and although the structure of the HAV capsid has been solved, it provides limited insights into the replication of HAV, and the role of the nonstructural protein in replication remains enigmatic. In this research proposal, we focus on HAV 2C protein: 2C plays a central role in virus replication and participates in almost every aspect of the virus life-cycle, hence it is a potentially important drug target. In this project, we aim at: (i) investigating the functions of HAV 2C; (ii) determining its high-resolution structure; and (iii) validating the structural findings via mutagenesis. Knowing the structure of HAV 2C will allow virtual screening for drug leads, and should eventually assist in the development of antiviral drugs. Title: Uncovering developmental and transcriptional mechanisms of the early synthesis of cytotoxic, antimicrobial, and cardiotonic bufadienolides in toads Principal Investigator: Dr. Jennifer Lynn Stynoski, Clodomiro Picado Institute, University of Costa Rica, San JosĂ©, Costa Rica ICGEB Reference No. CRP/CRI19-04_EC Abstract: A class of steroids called bufadienolides have shown enormous potential as natural products to treat and diagnose cancer, microbial and fungal infections, preeclampsia, and heart disease..Bufadienolides are synthesised in the glands of toads as chemical defences against predators and pathogens, and have long been delivered in crude toad venom as traditional medicine, with diverse detrimental side effects. The development of these into targeted therapeutic tools is limited by a lack in our understanding of the biosynthetic and genomic pathways underlying the production and activities of bufadienolides in animal tissues. Using four different Costa Rican toad species, whose bufadienolides vary in their degree of toxicity, we propose to identify: (i) when and where bufadienolide biosynthesis starts and (ii) the changes in gene expression that are associated with their initial biosynthesis in toads. Understanding how changes in gene expression allow toad cells to make bufadienolides will give us the foundation necessary to research and produce specific therapeutic targets in transgenic models in the future. Title: Piperine for the prevention of breast cancer Principal Investigator: Dr. Rama Ibrahim Khalaf Mahran, Department of Pharmacology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt ICGEB Reference No. CRP/EGY19-04_EC Abstract: Breast cancer is the first cause of cancer deaths among the North African women, including Egyptian women. Prevention of breast cancer represents a cost-effective strategy, as an alternative to treatment. Piperine, the spice derived from black and long pepper, has been shown to have anti-carcinogenesis effects. We question whether piperine will effectively prevent breast cancer by targeting human dysplastic breast stem cells. The aims of this project are: (i) to evaluate the preventive efficacy of piperine against breast cancer in human cell line- derived mammary organoids; (ii) to learn how to establish primary human normal, dysplastic, and cancer 3D mammary organoid cultures; and (iii) to grow primary organoids in cultures in Egypt. Mammary organoids will be treated with piperine and the effects of piperine on stem cell self-renewal, stemness, viability, growth and proliferation, and differentiation will be tested. Finally, the molecular pathways by which piperine targets dysplastic stem cells will be identified. Title: Comparative lipidomics for development of Mycobacterium tuberculosis-based lipid biomarkers Principal Investigator: Dr. Feven Tigistu-Sahle, Ethiopian Biotechnology Institute, Addis Ababa, Ethiopia ICGEB Reference No. CRP/ETH19-05_EC
  • 3. Abstract: Mycobacterium tuberculosis (Mtb) is the causative agent for Tuberculosis (TB), a leading cause of death globally. A quarter of the global population is estimated to be latently infected with Mtb, meaning that their immune system can effectively contain this infection, to remain healthy. Of these latently infected individuals, fewer than 10% progress to active TB infection during their lifetime. Very little is known about the factors that determine these risks and there is lack of effective biological markers to differentiate the latent from active infections. Several studies have established the role of lipids in Mtb survival within the host environment and during its progression to the active state. This project aims to use modern analytical methods to compare the lipid profiles of Mtb at different stages of infection, to identify novel lipid molecules for use as biomarkers. The discovery of reliable biomarkers will advance treatment options through the rapid and accurate identification and differentiation of individuals with latent and active Mtb infections. Title: Examination of the interaction between Candida and oral squamous cell carcinoma cells on the level of extracellular vesicles Principal Investigator: Prof. Attila GĂĄcser, Department of Microbiology, University of Szeged, Hungary ICGEB Reference No. CRP/HUN19-01 Abstract: According to our previous findings, oral squamous cell carcinoma (OSCC) patients are characterised by having increased yeast abundance in their oral cavity, compared with healthy individuals. Therefore, in this project we aim to explore the nature of an possible interaction, between local yeasts, (represented by Candida species) and oral tumour cells in vitro. Our purpose is to investigate yeast-tumour cell interaction at the level of extracellular vesicles (EVs), as EVs have recently been reported to be major mediators of intercellular (and inter-kingdom) communications. In this project, we also aim to thoroughly examine the physical interaction between tumour exosomes and Candida cells, as well as examining the effect of Candida EVs on OSCC cells. We plan to use OMICs analyses, biochemical assays, flow cytometry and microscopy experiments to better understand the molecular bases of the potential information transmission between fungal and cancer cells at the level of extracellular vesicles. Title: A molecular and immunological investigation of leishmaniasis from unusual foci of cutaneous and visceral disease in India and Nepal Principal Investigator: Dr. Manju Jain, Central University of Punjab, Bathinda, India ICGEB Reference No. CRP/IND19-01 Abstract: Leishmaniasis is caused by transmission of the Leishmania parasite through the bite of infected sandflies, which results in Cutaneous Leishmaniasis (CL), causing skin lesions, and Visceral Leishmaniasis (VL), a deadly systemic disease. The different clinical outcomes result from the interplay between the infecting Leishmania species and the host's immune status. Recently, the disease has spread to newer areas, where it shows atypical characteristics: such that the Leishmania donovani species, which typically causes visceral disease (VL), now causes cutaneous disease (CL). We propose to study two, newly-emerging, atypical foci of leishmaniasis - one in Himachal Pradesh, India, and the other in the western Hilly and Terai regions of Nepal - to understand why L. donovani has changed from being a deadly VL-causing parasite to being a less dangerous CL-causing parasite. L. donovani will be isolated from cutaneous lesions in these areas of India and Nepal, and genome sequencing will be performed to identify gene variants that may be associated with atypical cutaneous disease. Immunological correlates in VL and CL patients will also be investigated. Title: Determination of signal flow in cellular systems using the yeast fat regulating network as a model Principal Investigator: Dr. Bader F. Al-Anzi, Kuwait Institute for Scientific Research, Safat, Kuwait ICGEB Reference No. CRP/KWT19-01 Abstract: We have used genetic, proteomic and physiological methods to characterise a protein network that regulates fat storage in yeast. In this network, the contribution of a given structure to its overall signalling output can be determined by simply measuring fat in cells missing that structure. Thus, it can provide empirical parameters to computationally model signal flow within a cellular network. We have succeeded in showing that the importance of each protein to network output is dependent on a topological parameter called Katz centrality. However, it is also important to establish the amount of signalling carried by individual protein connections. To rephrase what we are attempting to do: if these connections are highways, how much traffic are they carrying? This goal will be achieved by following a multidisciplinary approach utilising Mass Spectrometry, yeast strains that cannot form a given protein connection, a variety of metabolic assays, and computational analysis. The acquired data will be used to build a predictive signal flow model. Title: CRISPRi genetic screen in identifying surfaceome addiction in glioblastoma multiforme Principal Investigator: Dr. Mohamad Aimanuddin Mohtar, UKM Medical Molecular Biology Institute (UMBI), UKM Medial Centre, Kuala Lumpur, Malaysia ICGEB Reference No. CRP/MYS19-04_EC Abstract: Glioblastoma Multiforme (GBM) is the deadliest disease of the central nervous system. GBM-diagnosed patients have a low survival rate, averaging 12-15 months’ life expectancy. Current standard-of-care therapies have provided poor efficacy in treating GBM. Our analysis, utilising the public genomics database, revealed that many genes encoding the cell surface proteins (termed surfaceome) are highly expressed in GBM, suggesting their importance in GBM pathogenesis. Thus, the general aim of this study is to identify novel oncogenic drivers within the cell surface sub-proteome that support GBM growth and progression. This will be achieved via the utilisation of a CRISPRi genetic screen targeting the most significantly upregulated components of the GBM
  • 4. surfaceome. The candidate hits from the screen will be functionally validated using cell-based and mouse model experimental assays. This study will facilitate the discovery of novel oncogene addictions in GBM that could potentially be targeted in the clinic, either individually or as part of a combination therapy. Title: Paleogenomic characterisation of human pathogens spanning the Native-European contact in Latin America Principal Investigator: Dr. MarĂ­a C. Ávila Arcos, International Laboratory for Human Genome Research, National Autonomous University of Mexico, QuerĂ©taro, MĂ©xico ICGEB Reference No. CRP/MEX19-03 Abstract: Understanding the genetic makeup of pathogens involved in major pandemics is crucial for informing strategies to face the potential devastating effects of a reintroduction. Ancient DNA studies have revealed the causes of major epidemics and the genetic makeup of some ancient human pathogens. This is of interest in places like Mexico and Argentina, where a large fraction of the Native population died as a consequence of devastating outbreaks caused by pathogens introduced during European colonisation, some of which still pose epidemiological threats today. In this project we will (i) extract ancient pathogen DNA from archaeological remains from Mexico and Argentinian Patagonia to reveal the extent of pathogen diversity present in each region, before and after European colonisation; (ii) reconstruct whole genomes and resolve their phylogenetic relationship to other strains to unveil the evolutionary patterns of endemic versus introduced infectious diseases; (iii) identify genomic changes associated woth pathogenicity and host-pathogen interactions in the ancient strains. Title: Next generation diagnostics and characterisation for emerging viruses and virus-like agents of pome and stone fruits in Montenegro Principal Investigator: Dr. Jelena Zindovic, Biotechnical Faculty, University of Montenegro, Podgorica, Montenegro ICGEB Reference No. CRP/MNE19-01 Abstract: New emerging viruses and virus-like pathogens, as well as new variants of existing pathogens, pose a serious threat to agricultural production. The availability of metagenomic analyses through Next Generation Sequencing (NGS) has made accessible whole plant and pathogen genomes, and has become a powerful tool in the diagnosis of unknown plant diseases. The goal of this project is to acquire the knowledge, skills and competences in using the state-of-the-art NGS technologies to detect and characterise existing and emerging viruses and virus-like agents of pome and stone fruits, and to contribute to the development of their disease management in Montenegro. Title: Diagnostic, prognostic and predictive biomarkers for bladder cancer management Principal Investigator: Prof. Zivko Popov, Research Center for Genetic Engineering and Biotechnology “Gorgi D. Efremov”, Academy of Science and Arts of the Republic of North Macedonia (MASA), Skopje, North Macedonia ICGEB Reference No. CRP/MKD19-02 Abstract: Bladder cancer (BC) is one of the most common types of cancer worldwide, and molecular defects associated with the initiation of the carcinogenic process in this type of tumour has great clinical importance. Different molecular changes have been found in the tissue samples of patients with BC, which could be used as markers for non-invasive early diagnosis, as well as being potential prognostic and/or predictive biomarkers for patient management. The main aim of this project is the determination of the molecular (DNA, RNA, protein) changes in the early stages of the disease, present in the tissue and/or blood or urine of patients with bladder cancer. The potential use of the observed molecular changes as diagnostic, prognostic and predictive markers for clinical management of this disease will also be evaluated. Title: Design and test of in vitro and in vivo applicators for the use of electromagnetic energy against the Malaria parasite Principal Investigator: Dr. Lorena Michelle Coronado, INDICASAT AIP, Panama City, Panama ICGEB Reference No. CRP/PAN19-01 Abstract: Or group has successfully develped the use of microwave non-thermal irradiation in in vitro tests as a potentially effective malaria treatment, acting by inhibiting the growth of the causative parasite, P. falciparum..We are now at the challenging point when it is necessary to design and build applicators for the delivery of this energy in an effective and safe way in vivo. To achieve this task it is necessary to study the dynamics of blood movement using a fluid moving setup that simulates real blood circulation, with the application of microwaves at a given point of the circulating system. When the right parameters to achieve killing are achieved, tests will be carried out on mice infected with malaria. Our objective is to design, build and optimise applicators for the treatment of malaria using electromagnetic energy. The aims of this project are: (i) to design and test an applicator to be used against P. falciparum, based on parallel plates; (ii) to design and test an applicator to be used against P. falciparum, based on constant fluid; and (iii) to test the applicators against malaria in an in vivo model. Title: Are prion (PrP) and MARCKS proteins functional partners in vivo? MARCKS proteins as potential components of prion and Alzheimer’s neurodegenerative pathways Principal Investigator: Prof. Edward MĂĄlaga-Trillo, Universidad Peruana Cayetano Heredia, Lima, Peru
  • 5. ICGEB Reference No. CRP/PER19-02 Abstract: Alzheimer’s, Parkinson’s and prion diseases result from the cunning ability of toxic proteins to hijack biochemical signals normally used by neurons to communicate. One such signalling pathway involves the modulation of cell adhesion and neurotransmission by the prion protein (PrP) and its control over Src family kinases (SFKs). This mechanism is only partially understood, as PrP can interact with other molecules whose involvement in neurodegeneration remains unclear. Among these, MARCKS proteins are of special interest because, like SFKs, they associate with neuronal cell membranes and participate in the control of cell adhesion and neurotransmission. This proposal assesses the potential role of MARCKS proteins as, as yet unrecognised, downstream mediators of PrP neurotoxicity, complementary to SFKs. Using a combination of genetic, cell biological, biochemical and behavioural approaches in zebrafish embryos, we will examine the formation of functional PrP/SFK/MARCKS complexes, their involvement in neuronal physiology and their contribution to prion and Alzheimer’s neurodegeneration. Title: Development of bacterial inoculants for biological control of plant pathogens Principal Investigator: Prof. Djordje Fira, Faculty of Biology, University of Belgrade, Serbia ICGEB Reference No. CRP/SRB19-02 Abstract: Biological control of plant pathogens has become an important alternative to the extensive use of chemical pesticides in modern agriculture. The aim of the proposed project is to identify the best strains for the formulation of biocontrol inoculants from the existing laboratory collection. In our previous work, we have already characterised several strains of genus Bacillus at a genetic and biochemical level, including the basis of their strong activities against important fungal and bacterial plant pathogens in experiments both in vivo and in situ. Therefore, the focus of our research will be on several objectives: (i) to test the biocontrol capacity of selected strains in greenhouse and field trials on crops most important for Serbian agriculture; (ii) to expand the existing collection with Gram-negative bacteria, including their molecular and biochemical characterisation and determination of anti-pathogenic activity; and (iii) metagenomic studies of plant samples during their treatment with biocontrol agents, in order to determine the dynamics of plant microbiome and its influence on plant growth. Title: Regulation of intracellular complexes formed by dipeptide repeats from C9ORF72 mutation Principal Investigator: Dr. Boris Rogelj, Faculty of Chemistry and Chemical Technology, University of Ljubljana, Slovenia ICGEB Reference No. CRP/SVN19-03 Abstract: Progressive neuronal loss is a key feature in several forms of dementia and movement disorders. One signature microscopic feature that can be observed post-mortem in the brains of patients diagnosed with these diseases, is the abnormal aggregation of certain proteins. In Frontotemporal Dementia (FTD) and Amyotrophic Lateral Sclerosis (ALS) this protein is TDP-43. The most common mutation in ALS and FTD is in the C9ORF72 gene and leads to disease causing aggregations of TDP-43. The mutation in C9ORF72 gene results in formation of toxic RNAs or proteins, whose direct linkage with the disease still needs to be determined. With this proposal we aim to identify the set of proteins that interact with C9ORF72 toxic proteins in living cells, to examine whether the interactions lead to TDP-43 aggregation and to determine how these interactions could be used to attenuate their toxicity. Title: ValitaCHO: Faster and cheaper manufacturing of biopharmaceuticals using next generation “super” CHO cell lines generated using a novel directed evolution and synthetic biology strategy Principal Investigator: Dr. Deepak Balaji Thimiri Govinda Raj, CSIR Biosciences, Pretoria, South Africa ICGEB Reference No. CRP/ZAF19-05_EC Abstract: The biopharmaceutical industry is rapidly growing and is crucial to the well-being of global citizens. Biotherapeutics offer significant advantages and we now have the theoretical toolkit to treat almost all diseases. Significant challenges exist in transferring it to a viable solution. Currently over 70% of the commercial biotherapeutics are manufactured using Chinese Hamster Ovary (CHO) cells, but it is widely acknowledged that in their current format this is unlikely to continue. As the complexity increases, the economics of current CHO- based biomanufacturing further deteriorates and, as we prepare for more futuristic applications, the CHO expression system needs to be significantly improved or to be completely replaced. The key objective of this project is to generate "super" CHO cell lines for improved biopharmaceutical production. Herein, we describe an approach to utilise all of the knowledge generated to date on CHO cells and to evolve this to develop a cell line more fit for purpose, in terms of both cost and production capacity. Title: Comparative study of Sickle Cell Disease modifiers in Ghana, Nigeria and Tanzania. Investigation of foetal haemoglobin parameters and clinical manifestation Principal Investigator: Dr. Siana Nkya, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania ICGEB Reference No. CRP/TZA19-01 Abstract: Sickle Cell Disease (SCD) is an inherited blood disorder that is caused by a mutation leading to the synthesis of abnormal haemoglobin and red blood cells (RBC). SCD is clinically characterised by insufficient blood (anaemia), episodes of pain, painful swellings of the hands and feet, frequent infections and delayed growth. SCD patients inherit the sickle mutation with other genetic combinations, which are known as haplotypes. Five SCD haplotypes have been described: Senegal, Benin, Central African Republican, Cameroon, and Arab-Indian. SCD symptoms are different among individuals with different haplotypes.
  • 6. Foetal Haemoglobin (HbF) is a major modifier of the severity of SCD symptoms; however the levels and distribution of HbF in RBCs is different among individuals with SCD and across SCD haplotypes, leading to the observed differences in SCD symptoms. This study will be one of the first in Africa to systematically compare HbF levels and distribution with clinical symptoms across SCD patients from different geographical locations and with different SCD-haplotypes. Title: The synthesis and testing of novel drugs for the treatment of Diabetes Mellitus Principal Investigator: Dr. Varma Hemant Rambaran, The University of Trinidad and Tobago, Arima, Trinidad and Tobago ICGEB Reference No. CRP/TTO19-01 Abstract: Present anti-diabetic medicines on the market still rely on the signalling action of insulin as a means of remedying the hyperglycemic levels in the body. This is a major problem in the case of Type II Diabetes, where the cells’ insulin receptors have become desensitised to the action of insulin and therefore an alternative form of therapy is needed. Vanadyl complexes have had a successful history, as insulin mimetics, in attenuating blood glucose levels, however, a shortcoming is the gastric disorders that are associated with oral administration. To overcome this disadvantage,, it has been proposed that a means to avoid such deleterious effects is to optimise or change the specie of binding ligand. The project discussed herein focuses on the synthesis and biological evaluations of two novel vanadyl complexes, with the hope of obtaining at least one drug that will be both pharmacologically effective and safe when used as a diabetes-therapeutic agent. Title: CD300f immune receptors in neuroinflammation and neuroplasticity: role for behavioural alterations relevant for major depression disorder Principal Investigator: Dr. Hugo Peluffo, Institut Pasteur de Montevideo, Uruguay ICGEB Reference No. CRP/URY19-01 Abstract: Depressive disorders affect more than 350 million people worldwide. Recently, increased immune responses and higher levels of inflammatory molecules have been found in depressed patients. The immune system is our defence system, being responsible for identifying and protecting the body against potential threats. However, dysfunctional immune activation after stress exposure can be detrimental, and a condition called neuroinflammation may impact the function of, and communication between, brain cells in areas responsible for controlling behaviours, such as mood and pleasure/reward. Our goal is to study the receptors for CD300f, a molecule present in both immune and brain cells, which is involved in the control of immune activation and in reduction of inflammation. We will use genetically modified mice and human studies to investigate whether CD300f receptors can control the spread of neuroinflammation, and the changes in brain cells, and resultant behaviours relevant for depression. With this knowledge, we can propose new pharmacological strategies to treat depression. Title: Characterisation of a GWAS-derived QTL for yield-related traits in Vietnamese landraces suitable for local rice breeding program Principal Investigator: Dr. Ngan Giang Khong, Agricultural Genetics Institute, Hanoi, Vietnam ICGEB Reference No. CRP/VNM19-03 Abstract: Panicle architecture is one of the key components of rice yield and exhibits a large diversity. To identify the morphological and genetic determinants of panicle architecture, a genome-wide association study (GWAS) using an original panel of Vietnamese landraces, was performed. Twenty-nine stable QTLs associated with several panicle traits were detected over the two years. Interestingly, a new single QTL with co-location of both Spikelet Number (SpN) and Secondary Branch Number (SBN) traits was observed (namely QTL_9), and no functionally characterised genes were co-located in this genomic region of 780 Kb. The aim of this project is to characterise the GWAS-derived QTL9 and the associated genes related to rice yield. The main objectives are: (i) to characterise the QTL9 through bi-parental population; (ii) to analyse the function of candidate genes in Vietnamese varieties by transgenic plants; and (iii) to develop the genetic markers for rice breeding programmes in Vietnam.