The Telegraph
| Monday, November 7, 2016 |

Knowhow

Bloody good

Indian scientists have recently found how blood cells are produced in fruit flies, something that had been undiscovered in the 100 years the fly has been studied. T.V. Jayan reports

The excitement oozes out with every word she speaks. And biologist Lolitika Mandal has every reason to be elated. After all, what her team at the Indian Institute of Science Education and Research (IISER) in Mohali has achieved is nothing less than path-breaking in the field of fundamental biology. Not just that, it may even bring in a paradigm shift in how several early-age blood disorders are studied and treated.

The IISER team, which includes her husband Sudip Mandal — who is also an IISER faculty member — resolved an enigma that has puzzled biologists for many years. They unravelled how a certain class of stem cells — that differentiate into blood cells — are created in fruit flies (drosophila). Elucidating the origin of stem cells that produce blood cells in fruit flies can have profound impact on medical research.

Fruit flies, which have an average lifespan of 45 days, may seem very different from us but their basic cell machinery, development and gene regulatory processes are remarkably similar to humans. As a result, scientists consider fruit flies an ideal and convenient model to study human diseases as well as to unravel fundamental genetic and cellular mechanisms. To do this, researchers develop fly models by either manipulating fly genes to simulate the disease conditions or creating transgenic flies that carry the human disease-causing mutant genes.

  • Lolitika Mandal (centre) with students Parvathy Ramesh and Nidhi Sharma Dey (right)

The development of blood cells (or haematopoiesis) in humans is directly linked to many diseases. Early onset leukaemia and Fanconi anaemia are two diseases that take root during the early days of blood cell formation.
Although the studies in the last decade had indicated that the process of blood cell formation in mammals, including humans, evidences for the existence of blood forming stem are lacking. The IISER work, reported in the journal eLife in the last week of October, solved this mystery. It not only identified the stem cells from which these blood cells originate but also unravelled the molecular mechanism at play.

“What this means is that if we have a good understanding of how these blood cells originate in fruit flies, then these insects can be used as a good experimental model to study the early onset of blood disorders,” explains Mandal, who is a developmental geneticist at the IISER. The first author of the study, is Mandal’s doctoral student Nidhi Sharma Dey.

“Studying stem cells that give rise to blood cells is difficult (and unethical) in humans because they are present only during the early days of the foetus. Similar attempts in animal models such as mice also yielded very little,” says Mandal, who hails from Asansol in West Bengal. According to her, all our understanding about different kinds of human stem cells (such as cardiac, brain or germline stem cells) has come from drosophila models. But similar studies could not be carried out on blood stem cells as scientists had not been able to identify similar stem cells in fruit flies.

The IISER team not only identified the source of stem cells that differentiate into blood cells in the fly but also unearthed the cellular machinery that is required for their differentiation.

“This work is significant as it provides insights into the evolutionary history of blood progenitor cells (cells that differentiate into blood cells). Understanding the genesis of blood using organisms like fruit fly will help us understand molecular pathways associated with this process,” says L.S. Shashidhara, a renowned developmental biologist at IISER Pune.

Agrees Gaiti Hasan, a biologist with the Bangalore-based National Centre for Biological Sciences who has been using fruit flies as an experimental model. If the signalling mechanisms identified by the study serves the same or similar function during human blood cells formation, it can help identify ways to control or regulate blood cell formation in humans, says Hasan. “This would then be of obvious significance in finding ways to treat blood diseases,” she observes. 

It is not the first time that Mandal has dared to challenge conventional wisdom. Last year, her team surprised the scientific community when they demonstrated that blood cells are formed in fruit flies even when they are adults. As per the prevailing understanding, blood cells in the body of a fruit fly are formed only during embryonic or larval stage.

Even though fruit flies have been a subject of study for more than 100 years, the predominant view till very recently was that all cells in a fly body, except those responsible for reproduction, are formed during the embryonic or larval stage and no cell division occurs afterwards. Progenitors of blood cells in a fruit fly in particular were thought to be produced during larval and pupal stages and seemingly had no capacity to divide during the adult stage.

To challenge this, Mandal’s team then asked a fundamental question; if they do not produce new blood cells how do these insects survive basic hazards of life, say a bacterial infection that requires a quick and spontaneous immune response. In vertebrates, such a threat is tackled by different types of blood cells that get routinely regenerated. This enquiry led to the identification of hubs where progenitor blood cells are formed. Named haematopoietic hub, the site was found to be very similar to the bone marrow of vertebrate animals, they reported in a paper published in Developmental Cell.

“With our latest findings we have been able to find answers to the most important queries that have been bugging this field (blood cell formation),” says Mandal.

With this, medical scientists may now hope to get a better handle on treating human blood diseases.