Dr. Rachel Matar Explains Research Activity of AURAK’s Biotechnology Department

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Dr. Matar received an M.S. in Bioinformatics, Structural Biochemistry and Genomics from the Mediterranean University, Marseille, France and a Ph.D. in Structural and Functional Biochemistry from Claude Bernard University, Lyon, France. Prior to coming to AURAK, Dr. Matar worked as a researcher and faculty at the Unit of Drug Resistance Modulation and Mechanism, Institute of Biology and Chemistry of Proteins, CNRS, Lyon, France.

What are the different research fields in your department?

In the Biotechnology Department, we have two different areas of research: Biomedical and biofuel.

In the medical field, we are focusing on cancer biology, developing and identifying novel potent molecules either from natural or synthetic origins as anti-cancer agents. These studies involve investigating cytotoxic, DNA damage and cell death mechanisms using pre-clinical systems. Our aim is to develop potent drugs, especially against multi-drug resistant breast cancers. Exploring novel compounds as potent anti-cancer agents implies a great asset to current knowledge in the field and possibly to develop effective therapeutic regimens by using these molecules alone or in combination with other drugs so that they can reduce cancer growth. In parallel, we are working on dissecting the crosstalk between cycle cell proteins and cell death pathways, and the regulation of calcium signaling pathways during cellular pathology in models of kidney injury and cancer.

In addition, we are also working in the field of immunology, where we are studying Siglecs and sialic acids. Sialic acids are monosaccharides that are expressed at the end of the sugar chains in proteins and lipids. Siglecs are the proteins that bind with these monosaccharide sugars. These proteins are present on immune cells in our body and any dysfunction in them leads to diverse disease conditions such as Alzheimer’s disease, cancer and sepsis.

In the biofuel field, we are isolating fungi from the mangrove wetland of Ras Al Khaimah. The fungal cell mass of these isolates is evaluated for its lipid quality and quantity for biodiesel production. When carbon is in excess and a key nutrient such as nitrogen or phosphorous is limited, oleaginous fungi store high levels of lipids. These stored lipids or Single Cell Oils (SCOs) are accumulated as intracellular lipid bodies (LBs). LBs varying in size, number and shape are characterized. Potential biodiesel fungi are assessed based on two   important steps:

1. Characterization of oleaginous fungi
2. Intracellular lipid bodies determination in oleaginous fungi.

Are these active areas of research worldwide? Which universities or research groups are leading these research efforts? How does research in these areas connect with research in other fields?

Cancer biology, drug discovery, immunology, molecular and cellular biology and biofuel are essential for advances of interdisciplinary biomedical sciences as well as renewable energy. These areas of research are very active worldwide where multiple research groups at MIT, Harvard and several other top-ranked universities across the world are focused on them.

As a biologist, can you give us your view on the COVID-19 situation? How did it originate? What is the difference compared to other viral infections? What research is being done to address this pandemic worldwide? How often should we expect such pandemics?

COVID-19 stands for COronaVIrus Disease 2019. It originated in the Wuhan province of China in December 2019, where it is supposed to have started from a seafood market in the Huanan region. It is believed that people consumed food from this wholesale seafood market and got contaminated with a novel species of coronavirus called SARS-CoV-2. The affected people showed very high human-to-human transmission. Initially, around 59 suspected cases of viral infection were isolated in a hospital in Wuhan and were tested. It was found that 41 out of those were positive for SARS-CoV-2, but this isolation process was too late and the virus had already been transmitted to      thousands of other people who were in close contact with these 41 individuals. Since it was the time of Chinese New Year, people from China also travelled to different countries and thus affected many other people in the world, and it spread globally, affecting more than 193 countries. This was the origin of the COVID-19 pandemic.

COVID-19 symptoms may appear 2-14 days after infection. Most people will develop mild to medium symptoms similar to influenza, like fever, headache, and dry cough, and recover without treatment; however, it can progress into serious illness especially in older people and those with preexisting medical problems or low immunity. Critically ill patients develop pneumonia and suffer from respiratory failure.

The major difference between COVID-19 versus other viral infections is that the causal agent for COVID-19 is a new virus that has transmitted from an animal (bat), which the human immune system has never seen before. Moreover, unlike other viral infections, there is no vaccine or medicines for COVID-19. If we compare COVID-19 with other viral outbreaks of the recent past, there are several differences. The Severe Acute Respiratory Syndrome (SARS) started in 2002, infected 8,000 individuals and killed 774 people. It was contained earlier because the disease was only being transmitted after the appearance of the symptoms. On the other hand, COVID-19 cases can be asymptomatic, and these carriers of the disease can transmit it.

Middle East Respiratory Syndrome (MERS), which appeared to be caused due to association with camels, started in 2012. The death rate of MERS was around 30-35%, but person-to-person transmission was very low. Therefore, just like SARS, the global pandemic situation did not arise. Another viral outbreak that started was Ebola in 2014, where the death rate was as high as 80%, but it does not transmit through respiratory droplets; instead, it spreads through a bodily fluid such as blood, sweat, feces, etc. Moreover, Ebola has very severe   symptoms. Therefore, person-to-person transmission is not as high as COVID-19. The last one we can talk about is influenza, which is not novel. Even the H1N1 outbreak of 2009 had some unique components, but still it was not absolutely novel. Our immune system had seen the influenza virus before, so we have immunity against it. Moreover, we have a vaccine against influenza and medicine (Tamiflu) against it.

Studies on SARS-COV-2 are promptly starting and the knowledge about COVID-19 is swiftly accumulating. These research studies include molecular analysis of the viral genome and replication cycle, its transmission route, interaction with human host cells, antiviral drugs, and the anticipated vaccine. Initial studies on specific antiviral drugs using artificially grown human cells have shown promise in test-tube experiments with human lung and airway cells. In parallel, the clinical trials were initiated in a record time to study potential drugs as a cure to stop progression of the disease.

In the last 20 years, we have seen several viral outbreaks, and we can expect to see more. The reason behind this is the fact that animals host several viruses on and inside their bodies. Close contact with these animals transmits the virus to human beings. Several of these viruses are still unknown and may have the ability to cause severe diseases. Therefore, in my opinion, this is not the last pandemic the human race is seeing, but this experience will certainly help us to prepare better for the next one.

How do you see the effect of this pandemic on the future research and applications of biotechnology? And how can we develop new programs coping with these new directions?

Biotechnology can be better described as the driving force behind applied biology, which in turn is an inevitable domain in translational medicine. With every pandemic we clearly perceive the importance of biotechnology in   unleashing the new discoveries that could save our lives. With the current pandemic and with almost every pandemic, the impact is not restricted to research on infectious diseases, but rather it extends to affect several other areas and this is due to the complexity of these diseases and the requirement to tackle such problems from different angles. For example, the current efforts for developing a cure for COVID-19 are focused on finding a drug and most probably a spectrum of these to minimize pathogenesis with minimal side effects. These studies involve multiple areas in biotechnology such as genetic engineering and drug discovery, genomics and proteomics tools to unlock complex viral host cell interaction, and developing new ways of diagnosis.

The fact that investing in medical biotechnology research and developing life-saving solutions have positive correlation reflects the importance of funding interdisciplinary research that encompasses all aspects of microbial pathogenesis, innovative treatments, and vaccine development. Launching advanced academic programs such as molecular biotechnology, medical and pharmaceutical biotechnology, microbial biotechnology, and biomedical engineering will be in demand to address the future challenges in public health.

How about the research agenda of the department? What has been the focus of research in recent years? What is the potential impact of this research?

1.  We are working on developing and identifying novel potent molecules either from natural or synthetic origins as anti-cancer agents. In line with these drug discovery strategies, we identified the scope of using flavonoids for treating different cancers and inflammation. We have successfully published some of our findings and more are to follow in the near future.
2. In addition, we are working on a project to overcome the resistance of cancer to chemotherapy by chemo sensitizing the tumors using a combination of cancer drugs and modulators that can block a group of ABC transporters known to be overexpressed in advanced cancer stages. The drugs combination is used to overcome the multi-drug resistance phenotype created by this group of transporters.
3. We are studying a family of proteins called Siglecs (Sialic acid-binding IgG-like lectins). These are mainly expressed on the immune cells but recently they have been found to be expressed on non-immune cells also, such as cells in the brain. We recently published a paper in the journal “Cells” entitled “Siglecs in brain function and neurological disorders.” In this paper, we discussed how Siglecs’ expression is a modifier of several neurological disorders. This research has a lot of impact because there is no cure for many such disorders, including Alzheimer’s disease. Since Siglecs appeared to be a modulator of Alzheimer’s, therefore it is now considered to be a therapeutic target. In addition, we are beginning to understand the role of Siglecs in schizophrenia, multiple sclerosis and other disorders too. This research will give impetus to therapeutic interventions for such diseases.
4. We are also focusing on the link between cell cycle and cell death pathways in cellular disease models of kidney injury and cancer. Our major goal is to understand at the molecular level the mechanisms contributing to cell fate. This will provide a better understanding of the pathophysiology of the related disease. Importantly, this may help in designing new therapeutic interventions and minimize negative side effects of approved existing therapies.
5. The biotechnology team has published several papers on gene therapy and the use of nanoparticles to create a customized medicine to treat cancer as well as many genetic diseases. Gene therapy is the use of genes to heal diseases at the genetic level. It involves insertion, correction or inactivation of specific genes in organisms suffering from genetic disorders. Ever since it was introduced as a hypothesis in the 1960s, gene therapy has gone on to become a medical wonder that promises relief from different diseases like Parkinson’s disease and multiple sclerosis.
6. In the field of renewables, we are analyzing the abundant microorganisms in the naturally occurring mangroves of Ras Al Khaimah in the United Arab Emirates (UAE), and the feasibility of a future where the emirate invests in biofuels sourced from its mangroves as opposed to using conventional methods of fuel production and usage, which can have negative impacts on the environment and economy. We found that currently it is possible to use the existing mangroves as a source of fungi for biofuel production, but more investment is needed to support industrial-level production. We are implementing long-term energy solutions that address the UAE’s environmental and economic concerns, and encouraging future leaders and innovators to think local in addressing global problems.

List of relevant publications:

• Merheb M, Matar R, Hodeify R, Siddiqui S.S, Vazhappilly C.G, Marton J, Azharuddin S, AL Zouabi H. Mitochondrial DNA, a Powerful Tool to Decipher Ancient Human Civilization from Domestication to Music, and to Uncover Historical Murder Cases. Cells 2019, 8, 433
• Vazhappilly, C.G.; Ansari, S.A.; Al-Jaleeli, R.; Al-Azawi, A.M.; Ramadan, W.S.; Menon, V.; Hodeify, R.; Siddiqui, S.S.; Merheb, M.; Matar, R. Role of flavonoids in thrombotic, cardiovascular, and inflammatory diseases. Inflammopharmacology 2019, 1-7.
• Siddiqui, S.S.; Matar, R.; Merheb, M.; Hodeify, R.; Vazhappilly, C.G.; Marton, J.; Shamsuddin, S.A.; Al Zouabi, H. Siglecs in Brain Function and Neurological Disorders. Cells 2019, 8, 1125.
• Merheb M, Matar R, Soleimani M, Marton J, Abou Youssef K, Rawad Hodeify, Shafiq N.(2018) Biodiesel feedstock exploration: Ras Al Khaimah mangroves. Policy Papers, Al Qassimi Foundation
• Matar R, Merheb M. (2016) Paleogeneticist view of leather: The role of mitochondrial DNA to uncover the mysteries of fake leather and its products. Biosci. Biotech. Res. Comm. 9(1): 6-14 (2016)
• Soleimani M, Al Zaabi A, Merheb M, Matar M. (2016) Nanoparticles in gene therapy. International Journal of Integrative Biology 17 (1), 7-16

Can you describe the Biotechnology Department’s involvement in externally funded projects and in collaborative networks with other researchers?

1. Increased demand for biodiesel has necessitated looking for alternative oil resources. Single cell oil produced through heterotrophic organisms having high oil content (oleaginous) is considered a highly attractive option. It has been reported that oleaginous microorganisms such as microalgae and fungi could produce microbial lipids of up to 20% or more of their cell mass. In the project funded by Sheikh Saud bin Saqr Al Qasimi Foundation for Policy Research “Biofuel Exploration from Soil Microorganisms in Ras Al Khaimah Mangroves” (April 2015- December 2016) we isolated fungi from the mangrove wetland of Ras Al Khaimah. The fungal cellmass of these isolates was evaluated for its lipid quality and quantity for biodiesel production.
2. Antibiotic resistance is a major threat to health and well-being worldwide. It leads to increased healthcare costs, extended hospital stays, and increased morbidity and mortality. The major reason for antibiotic resistance is the irrational use of antibiotics in the health system and in farming. In the research funded by Sheikh Saud bin Saqr Al Qasimi Foundation for Policy Research ”Resisting Antibiotic Resistance in Ras Al Khaimah” (2019) we focused on identifying the degree of negligence among the RAK public concerning the irrational use of antibiotics and to raise awareness of the impacts of such actions.  To accomplish this, we have dynamic experts from the Biotechnology Department at AURAK as well as from Ras Al Khaimah Medical and Health Sciences University (RAKMHSU) and Mohamed Bin Rashid University (MBRU), Dubai.In addition, we have written some project proposals and applied for external grants that are still under review. One of these projects is about how to make students smarter and enhance their learning abilities by making them play a diverse set of IQ strengthening games. In this project, we aim to create a freely available web portal that will provide a personalized prediction of IQ-enhancing video games to students for improving their learning skills. In this time of pandemic, when outdoor activities have been restricted and students need good options to utilize their time, this project is very relevant. In this project, we are collaborating with various departments such as AURAK’s Department of Computer Sciences, AURAK’s Department of Education, and the Department of Physiology of Ras Al Khaimah Medical and Health Sciences University (RAKMHSU).In the other project, we are trying to find out why innate immune cells remain quiescent (inactivated) in the bloodstream but when they reach the tissue, they become activated. This is particularly important because in bacterial infection of the blood, this control is lost and thus leads to systemic inflammation and death. In this project, we are collaborating with New York University Abu Dhabi (NYUAD).

How do you see the future of biotechnology in the UAE?

The vital role of biotechnology in addressing social challenges makes it an ever-developing field and thus it will continue to develop in the UAE and worldwide. The versatility of its applications in medicine, diagnostics, environmental sciences, and food security will speed up more investments in this field to include new academic programs and advanced research centers with cutting-edge technologies. This will eventually be reflected in a tremendous rise in job opportunities in the UAE and the region.