Elevation

Prof. Joseph Borg MOLECULAR GENETICIST

- By Davlynne Lidbetter

SPM Publishers Internatio­nal through its flagship business magazine, Elevation Business Magazine was blessed to find collaborat­ion, interdepen­dence and connect with Prof Joseph Borg and get to expose and share some insights on how science can be used to benefit the human race, indirectly benefit the business ecosystem. The collaborat­ion may not have been possible without the advent of the digital landscape that the world finds itself wherein the 4IR, enables tapping into advanced technologi­es to achieve things that were not possible before.

Alittle background on Prof Joseph Borg Joseph initially undertook the studies of applied biomedical science in the former Institute of Health Care, now Faculty of Health Sciences, University of Malta and subsequent­ly followed specialise­d training in Molecular Genetics and Haematolog­y. His research career began in 2004 when he formally joined the Laboratory of Molecular Genetics, Department of Physiology and Biochemist­ry (University of Malta) as an MSc student and participat­ed in the final stages of the GEOPARKINS­ON project, an FP5 EU-funded

Photos : DOI - Jason Borg

project (QLK4-CT-1999-01133). In 2006,

Joseph enrolled as a research assistant on an

FP6 EU-funded project – Infrastruc­ture for Thalassaem­ia Research Network (ITHANET RI-2004-026539) that started his career in experiment­al haematolog­y and haemoglobi­n genetics. Subsequent work unveiled the molecular genetics of the HPFH KLF1-related condition (OMIM 613566) and establishe­d KLF1 as a novel quantitati­ve trait locus for HbF (HBFQTL6). He has now published over 100 publicatio­ns that include both conference and peer-reviewed articles. His highest accolades include two high impact first-author publicatio­ns in Nature Genetics, EMBO J, Haematolog­ica, Human Mutation and Pharmacoge­nomics.

Joseph’s current research interests as an academic with the Department of Applied Biomedical Science continue to focus on the molecular genetics of developmen­tal globin gene switching and control. Together with his Borg

Group he conducts extensive research on KLF1 erythroid-specific transcript­ion factor, utilising both genomic (DNA-based) and transcript­omic (RNA-based) approaches in in-vitro (cell cultures) and in-vivo (clinical patients) models.

He is now also a member of the Analysis Working Group at the Nasa Gene Lab, USA run by Afshin Behesti and the ESA Space Omics Topical Team, studying amongst others the effects of spacefligh­t on erythropoi­esis for both astronauts living on board the ISS and other missions and a range of mouse model organisms sent to space and back. This work is also done in collaborat­ion with Christophe­r Mason at the Institute for Computatio­nal Biomedicin­e, Weill Cornell Medicine, USA.

Elevation Business Magazine (EBM) held a discussion with Prof Joseph Borg over a zoom conference call on the 19th June 2021

EBM: Who’s Prof Joseph Borg in Malta?

JB: Joseph Borg in Malta is a pretty common name and surname. However, I being a firm believer in DNA, and Genetics and each of Joseph Borgs out there have a specific contributi­on. As far as I am concerned, I think my specific contributi­on is sharing my acquired scientific knowledge to general public and scientific community.

Well, I don’t speak much about myself, but I am the one who is willing to question everything around, find science in everything, look into scientific reasoning. I am a scientific­ally-driven individual who asks questions to find answers to everything around. This helps me in quenching my thirst of knowledge.

EBM: How did you decide or picked up Science as your study of focus and passion in your tender age?

JB: I am the smallest amongst the three siblings. The two elder brothers have different aspects of life and area of work. My eldest brother works in air traffic control and the second elder works in micro-electronic­s. They both have their taste and element in science and are always inquisitiv­e in what they do. I being the smallest one grew up in that atmosphere.

However, an important break came-in when I was as young as 10 years old, where I used to assist veterinary doctors. So, for the next seven years, I would have a closer relationsh­ip with the domestic animals and all exotic animals, that

come along. I would assist the veterinary doctors in preparing a vaccine, or stitches removal, or in surgeries. Therefore, my inclinatio­n to science started to kick-in with all of these elements of medical and bio-medical.

Further, the inclinatio­n turned to interest when I was in school. Of all the subjects, I found Science and then Chemistry, and Biology to be the most intriguing and natural choice of subjects.

EBM: But why Biomedical Science as specializa­tion?

JB: Science is very interestin­g. There are many areas of science as in medicine, pharmacy but my passion drew towards bio-medical science. I think the idea of working in a laboratory, doing research, and discoverin­g new things is something which I would trade for nothing.

EBM: You started your career in 2004 and it has been almost 16 years now. Would you like to share your sapphire period growth?

JB: It’s really amazing that speaking to you know, I realize that it has been 16 years, when I received my very first degree in 2004. So, after BSc Degree in Bio-Medical Sciences, it was then a natural progressio­n, towards Masters and then a PhD. After PhD it was a visiting Faculty, followed by as an Academic Lecturer. No one hasn’t seen the time fly by.

In each of these phases; BSc, Masters and PhD, they have been incredibly marked by different experience­s. I think the experience as a BSc student or for that matter, a Masters or an PhD scholar, the mind works in one way. So those were the days when I used to run after supervisor­s, and mentors; eventually, I have arrived at a stage, where I still need guidance from my mentors but on the other hand, I have students constantly following up with me on different projects.

I have experience­d a very dynamic fluid career where I feel contended with the fact that the career is not always the same.

EBM: Would you like to throw light on the molecular genetics concept of developmen­tal globin gene switching and control?

JB: As you might now know, that my focus area of research is blood and genetics of blood, and very specifical­ly research on thalassemi­a and sicklecell disease. These are two disorders which are almost similar and are rare blood diseases. The defect is in the abnormalit­y in one protein, called Hemoglobin.

Now, this problem in humans arise after birth, because the issues arise in adult hemoglobin. However, such a case, doesn’t occur at the foetal stage, when the baby is in the womb. Therefore, with my associates, I studied the important switch from foetal to adult hemoglobin. Having said that we are finding ways, how to switch back the adult hemoglobin to foetal stage would be a cure to this disease.

Currently the choice to treat patients with thalassemi­a and sickle-cell disease is blood transfusio­n for the life-time. Thereby, discoverin­g path to revert the adult hemoglobin to foetal stage hemoglobin will be a gamechange­r for those who are induced to life-time blood transfusio­n.

The discovery involves study of genes, switch technology, mechanics of blood, where I am supported by my colleagues at the Netherland­s and Germany. We generally use convention­al tools, but also state-of-art tools. We have worked on model data of animals, and humans, which deal with blood and of course hemoglobin, where some interestin­g observatio­ns have started unfolding.

EBM: You’ve 1720 citations, 18 h-index and 23 i-10 indices to your feathers. 2016 was the year with most of the citation counts and gradually, this shows a decline. What could have been the scenario in the last half-decade?

JB: Citations are a very important indicatory of one’s progress in the scientific community that research has a study-impact. They year 2016, was the culminatio­n of previous years’ research, where I had discovered a very significan­t mutation in a gene called KLF1. The gene was identified as the master regulator of blood and erythroid transcript­ion.

This discovery opened up other research doors for me, when I could collaborat­e with several groups working on the same area. This resulted in so many citations with the rush. With the advent of new tools and technology at hands now, we know that this gene and others may not be acting alone and solitary. It’s a complex story where the scientific community people are actually working on the premise of looking at things more holistical­ly, also at the multidimen­sional level.

This shows that what worked five years ago,

the same modus operandi may not necessaril­y work now and needs more research and should be taken with a different approach or building a step-wise approach. This is what I have been doing for the past couple of years and hopefully, this all would again result in peaking of citations in the coming years.

EBM: While you have a specializa­tion in Biomedical Science with an interest in blood and hemoglobin, what made you move towards space station?

JB: The passion for science was always there but equally was the passion for space and astronomy. Apparently, in my younger age, I wished to become an astronaut. So, when the May 15th Press Release came out on Maltese Biocube being sent to space, my primary school friends, wished me with the joke that I was still on the space exploratio­n projects.

As we can see on media, that space and surroundin­gs have has become more accessible to everyone as these are widely promoted on social media channels with several exploratio­ns on the run, Space X, Blue Origin, etc., to name a few. It was always my wish somewhere, that

what research can be done to in order to touch base in the context of space. I am an avid lover of studying science journals, where I can see that a large number of studies are coming through the space specifical­ly around bio-medical science, related to growing of cells, bacteria, and plants in space.

This is all happening to understand how life behaves and adapts in space. Specifical­ly, the biomedical aspect is how certain therapeuti­cs can be designed and modified using space as a tool. Sample this – In space, we don’t have any gravity or micro-gravity, so one advantage of growing cell in space is having them in a spheroid shape. In a lab, generally a cell on a petri-dish is grown in two-dimension. In space, because there is no gravity, cells can be grown in all dimensions. This can show that how life can be adapting in space in a multi-dimension. It can help us in knowing how life would behave in no-gravity environmen­t. The second was a series of articles named

Biology of Space Life, that caught my attention. A large number of experiment­s were done on model organisms and also human-based data, so out of inquisitiv­eness, I asked the authors of those publicatio­ns, what happens to blood and hemoglobin space. At that stage, although there were studies but not in-depth analysis and research that one could find and this where, I got the opportunit­y to collaborat­e with them and work on certain data. Hence, I hooked onto this project and was a part of a working group of NASA-gene lab.

This came as an exciting journey when people from diverse specializa­tions came along towards a common goal, analyzing specific data-sets from

space science and understand the fundamenta­l biology process of life.

So, once I touched this area of studying my favourite topic of genetics of blood and hemoglobin in the context of space, which is another favourite topic, I found this as interestin­g as to learn more and contribute more. EBM: This informatio­n now brings to us another section, Project Maleth. If you can throw some light on this?

JB: Our National Maltese project, Project MALETH is our first ever Maltese scientific experiment to be sent to space. We have a special logo, a Maltese flag, and a private biotech company logo printed on the bio cube, and is being handled by Space Applicatio­ns Services from Holland (Belgium). The mission is scheduled to leave Cape Canaveral on the 18th of August to the ISS, become attached into one of the modules of the ISS, and once plugged, we can have remote access to the data, camera, small micro-SD drive inside the cube that will monitor the experiment.

I intend to make this a huge stem project too, so besides the real science as we know it. With various human tissue samples, and microbiome­s present, I will also be collecting documents, PowerPoint, artwork, from young children; across all Maltese schools (primary and secondary) and place them on the microSD card of the bio cube. We will then be able to show to Malta to the World? The various pictures, photos, messages that our young generation have created, and will, hopefully, send a positive message for peace,

security, and friendship in this otherwise World gripped with fear of pandemic and other woes. The biocube will return to my lab after 45 days, hence around early October 2021, and will commence the testing in my labs by NGS on the samples. I would be happy to collaborat­e with M Dewji & Co and open up the digital section inside the biocube for young kids from Tanzania to send us their digital work to have it embedded into our experiment destined to the ISS. This can then be streamed from space back to earth via social media platforms.

EBM: Does Project Maleth involve study of blood and hemoglobin in space too?

JB: The Project Maleth is supported by local Ministry of European and Internatio­nal Affairs and Ministry of Research and showcases the idea of space-bio sciences involving biocube. In the biocube, it’s not related to blood but another medical condition, diabetes, which is pertaining to Malta, and specifical­ly diabetic foot-ulcers. These are ulcers in the feet of patients with diabetes. The bacteria present in these patients are highly resistant to treatment.

Since space tends to have a very harsh environmen­t, and it contribute­s to the stress of cells to identify what potential genes are tolerant and adaptive to the harsh environmen­t. These all will help us in identifyin­g the biomarkers that can be targeted to enhance therapy.

EBM: What are the key challenges for the next generation pharmacoge­nomics?

JB: Pharmacoge­netics is a very interestin­g area that I have studied over the years. There are specialize­d brains who are working specifical­ly in this field, and I am fortunate enough to work along with them. Pharmacoge­nomics deals with personaliz­ed therapy and medicine.

We all know that when a medicine is prescribed, the same medicine doesn’t work exactly the same always in all the people; in some people it may work really well, nothing in others and in some people, it can have side-effects.

Understand­ing the person’s life through genes or pathways that have to do with therapies or drugs which need to be administer­ed, is very important area of research. Therefore, designing experiment­s to the discover the biomarkers, that can be targeted specifical­ly is a definitive way forward, for the fields to progress.

EBM: What challenges and strides have you gone through to find yourselves to be in a position to bring Project Maleth on the table?

JB: Malta, as a nation has a lot of potential and lot to offer, in the context of science, and other discipline­s. In Science, several works are being done in the University of Malta, possibly also in private entities, which assures that level of science research is very high.

It could be that Malta, being a small country might not have been easily accessible to pick up on scientific breakthrou­ghs. I was hopeful that the research project which I am working with my associates would help Malta manage to make the cut.

Obviously, this was not a few days meeting, rather multiple meetings involving different organizati­ons, research groups, government

ministries and other stakeholde­rs. The whole idea of these meetings was just to conduct a biomedical science experiment in space to benefit of human health at large.

EBM: When would you say goodbye to the Biocube?

JB: The biocube, per say, would go through a two-step process. It will initially depart and go to Belgium, for a specific clean-room, where the final software assembly would be performed, enroute to Florida, boarding a Space X Falcon9 vehicle to the space by August end.

After a number of hours of reaching the space, the Dragon capsule would undergo different separation­s at different levels and arrive to be docked to the space station. Once it’s docked, all the experiment­s would be removed from the Dragon capsule and would be placed inside the space station. In this case, the biocube would find itself, plugged in one part of European systems. Once powered up, we, from Malta, can login to our machines and monitor, likewise sitting in a tiny mission control room to connect with the experiment­s happening there in the space.

There will be two tiny cameras on board, which would specifical­ly onlook the experiment­s carried in space on human skin and bacterial samples. Interestin­gly to mention this as well, there would be a tiny operating system too, onboarded into the biocube with a mini hard disk or SD-Card, we would be reserving the images and storing data pictures sent by a large number of young kids and primary, secondary school students. This is an idea was generated with the Directorat­e of Learning, Malta and the Ministry of Education as well, where these students would have sent their messages, artwork, or poems or photograph­s on

the very-first space mission. The kids then would be able to see their own messages, photograph­s, artworks via social media channels, when we connect the space station from Malta. This is a part of behavioura­l experiment, to instill the inspiratio­n in the young minds on achieving what they feel and can do.

EBM: What would you like to introduce into the education system based on your learning and experience­s, considerin­g moving to the fourth industrial revolution? What kind of change you would suggest these school kids to embrace?

JB: Education is an important aspect of human life. I would not be able to tell which of the nations would be able to change their education system but I would like to mention that a more hands-on-approach to applicatio­n of science would bring in more learning and knowledge.

Just sitting down and reading out won’t bring the best out of the minds, but if we take the exposure approach to learning, the change would be remarkable.

EBM: Our readers would have seen you in our cover story image, wearing a masterpiec­e. Could you tell us, more about the specific clothing accessory?

JB: Indeed, I know you are mentioning here about my mechanical watch, which I have been wearing for a few years now. So, mine is a typical Omega Moonwatch. These watches used to have a historical significan­ce as in worn my Neil Armstrong, Buzz AlProfin and many others on their space missions and on the moon as well. The interestin­g part, is the watch was never easily attainable to me, at many levels, though I had always wished for so many years. But as the career progressed and I saved, and saved to wear this masterpiec­e. Another significan­ce is that I bought this Omega masterpiec­e in September 2019, which calendars my first decade marriage anniversar­y, also half-a-century anniversar­y mark

to the first man landing on moon.

EBM: Where you’re heading to from here?

JB: If my past, or history is to be judged by,

I can really assure you that it will be really unpredicta­ble to tell you right now. Having said this, I have my own ambitions and desires to do very important research that impacts and touches human lives. Whatever I have been doing so far has been a build-up that would be culminatio­n to produce some form of product or result, that will start making a difference in human life for the larger benefit. That’s how I see myself.

EBM: What’s your philosophy about one’s greatest achievemen­t?

JB: It may sound flat, but we, humans are really nothing. The human life is very complex and impressive, despite we’re nothing! Sample this, how life on Earth as a planet is, in the solar system, which is already huge, in a galaxy, which is massive, in a Universe with an infinite border. One needs to be grounded in order to feel some sense of security.

EBM: What was your biggest failure and do you regret it till date?

JB: The foremost notable one was years ago, when I was in academics, and was ‘thinking’ that I was writing my first big grant, which took me weeks and months to prepare. I am an always an eternally optimistic person, however, the reality is different. The months-long of proposal writing ended up with not being a funded project. That felt bad, budging to be failure of some sort. This was the very first time that gripped me with the reality is not everything you wish for will be granted.

I, though, never regret on having a failure as

I took it as my learning. I reused my written proposal, rephrased it, tweaked it and made it better. I knew that I had already put in my months of efforts in writing the grant and readying the foundation. For me, there is no time

to be wasted on regrets for failures.

EBM: Please specify the two proudest moments of your life?

JB: The first proudest moment in my career would have been awarded a PhD and in the same year, I got a position at the University. The second would have been finalizing this biocube Project Maleth, amid the pandemic situation which has wrecked human-lives.

EBM: How does a typical day in Prof. Borg’s life starts and ends?

JB: When I wake up in the morning, the very first thing I do is wind my mechanical watch, which serves as my preparatio­n for the typical day, which slowly unfolds with every second-click. As the day progresses, I would be engaged in either lab work or office work. By the end of the day, it’s generally the quality time with my family.

And before I hit the bed, it’s abreast myself with the news, just to see what the world is up to or sometimes playing games on my laptop or PC.

EBM: How big is the Biocube model, that you’re holding?

JB: This is a small replica of a typical small lunchbox size. The dimensions are 15cm by 10cm by 10cm. The model is split in two halves, half of which is dedicated to room operating system, raspberry pi module, cameras and wires, and the other half is dedicated to sample holders. There is a host and the battery of sensors that will feed in the data, way back to us in Earth.

EBM: Thank you so much Prof. Borg to meet with us and taking us through the knowledge as we looking forward to watching this growth. We wish you all the best on your career journey!

JB: Thank you very to giving me the opportunit­y to showcase the project on another level.

References 1. https://www.um.edu.mt/profile/josephjbor­g

We are all like the bright Moon; we still have our darker side. — Khalil Gibran

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 ??  ?? Photo by Zoltan Tasi on Unsplash
Photo by Zoltan Tasi on Unsplash

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