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The evolutionary history of ACE2 usage within the coronavirus subgenus Sarbecovirus

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Abstract

Severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) and SARS-CoV-2 are not phylogenetically closely related; however, both use the angiotensin-converting enzyme 2 (ACE2) receptor in humans for cell entry. This is not a universal sarbecovirus trait; for example, many known sarbecoviruses related to SARS-CoV-1 have two deletions in the receptor binding domain of the spike protein that render them incapable of using human ACE2. Here, we report three sequences of a novel sarbecovirus from Rwanda and Uganda that are phylogenetically intermediate to SARS-CoV-1 and SARS-CoV-2 and demonstrate via in vitro studies that they are also unable to utilize human ACE2. Furthermore, we show that the observed pattern of ACE2 usage among sarbecoviruses is best explained by recombination not of SARS-CoV-2, but of SARS-CoV-1 and its relatives.We show that the lineage that includes SARS-CoV-2 is most likely the ancestral ACE2-using lineage, and that recombination with at least one virus from this group conferred ACE2 usage to the lineage including SARS-CoV-1 at some time in the past. We argue that alternative scenarios such as convergent evolution are much less parsimonious; we show that biogeography and patterns of host tropism support the plausibility of a recombination scenario, and we propose a competitive release hypothesis to explain how this recombination event could have occurred and why it is evolutionarily advantageous. The findings provide important insights into the natural history of ACE2 usage for both SARS-CoV-1 and SARS-CoV-2 and a greater understanding of the evolutionary mechanisms that shape zoonotic potential of coronaviruses. This study also underscores the need for increased surveillance for sarbecoviruses in southwestern China, where most ACE2-using viruses have been found to date, as well as other regions such as Africa, where these viruses have only recently been discovered.

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Natural Sciences

Dr. Julius Mulindwa Wins DFG Research Grant

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The JICA Building, College of Natural Sciences (CoNAS) as approached from the Mary Stuart Road Roundabout, Makerere University, Kampala Uganda

Dr Julius Mulindwa, Lecturer in the Department of Biochemistry and Sports Science, College of Natural Sciences (CoNAS), Makerere University, together with colleagues Prof. Nicolai Seigel at the University of Munchen, Germany and Dr Kevin Marucha at Kisii University, Kenya were recently awarded a research grant by the German Research Foundation (DFG) amounting to 290,985 Euro. Out of this, 179,735 Euro is for the research activities that will be conducted at the Department of Biochemistry and Sports Science, CoNAS.

Dr. Julius Mulindwa, Department of Biochemistry and Sports Science, College of Natural Sciences (CoNAS), Makerere University.
Dr. Julius Mulindwa, Department of Biochemistry and Sports Science, College of Natural Sciences (CoNAS), Makerere University.

The research study is about, “Understanding cell to cell heterogeneity in African trypanosome field isolates”.

The benefits of this study to Makerere University will include:

  1. Capacity building in trypanosome single cell transcriptomics. This technic can be further exploited in other fields of research including cancer biology and it will be a great breakthrough if it is established at CoNAS.
  2. Training of a Ugandan PhD student and MSc students.
  3. Building research networks and fostering collaborative research between Makerere University, LMU, Germany and Kisii University, Kenya.  

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Research

17 Postdoctoral Research Teams Mentored as SECA Project Winds up

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Front Row: DVCAA-Prof. Umar Kakumba (4th L), Director DRGT-Prof. Edward Bbaale (4th R), Academic Registrar-Prof. Buyinza Mukadasi (2nd R) and Prof. Julius Kikooma (R) with Early-Career fellows and participants at the SECA Project Final Dissemination Workshop on 12th January 2022, Makerere University.

SECA is an acronym for the Supporting Early-Career Academics Programme at Makerere University (2019-2022). SECA is the fifth “phase” of the Carnegie Corporation of New York (CCNY)’s support to Makerere, and follows in the steps of similar successful initiatives that date back to 1946 when the Corporation’s relations with Uganda started. On Thursday 12th January 2023, the Deputy Vice Chancellor (Academic Affairs) and SECA Chairman Project Implementation Committee (PIC), Prof. Umar Kakumba was joined by the Director, Directorate of Research and Graduate Training (DRGT), Prof. Edward Bbaale as well as Academic Registrar and SECA Project Coordinator, Prof. Buyinza Mukadasi to preside over the programme’s final dissemination workshop.

Held in the Telepresence Centre, Senate Building, the workshop accorded the opportunity to research teams to present and discuss their findings. SECA supported seventeen (17) Early-Career academics at Makerere University, eight (8) of whom were female and nine (9) male, to undertake postdoctoral research fellowships in their respective fields of specialty. Additionally, SECA supported professional skills enhancement courses, as well as tuition and research costs for seventeen (17) Masters students (7 female, 10 male) attached to the research teams.

Furthermore, SECA provided funds to fellows for writing and publication, supported mentorship and research team building, provided travel grants to international conferences, and supported fellows to disseminate their findings to academia, policy makers and the general public. To facilitate improvements in the university research environment, SECA provided access to a grant worth US$6,000 to each of the fellows’ host departments. Some of the activities undertaken using the grants included; conducting academic writing and dissemination workshops, holding symposia for PhD students and academic staff, development of academic programmes, renovating research infrastructure and acquiring equipment.

Front Row: Prof. Umar Kakumba (C), flanked by Prof. Buyinza Mukadasi (L) and Prof. Edward Mwavu (R) listen to proceedings during the SECA Final Dissemination Workshop.
Front Row: Prof. Umar Kakumba (C), flanked by Prof. Buyinza Mukadasi (L) and Prof. Edward Mwavu (R) listen to proceedings during the SECA Final Dissemination Workshop.

Delivering his remarks, Prof. Umar Kakumba congratulated both Prof. Buyinza and Prof. Bbaale upon their new appointments as Academic Registrar and Director DRGT respectively, and thanked them for contributing to SECA’s success. In the same breath, he recognized and introduced members of the PIC namely; Prof. Jesca Nakavuma, Prof. Nicholas Kiggundu, Dr. Pamela Khanakwa, Prof. Julius Kikooma and Dr. Euzobia Baine Mugisha and thanked them for the rigorous work done in reviewing applications by fellows.

“I wish to congratulate you the fellows. As part of the monitoring team for SECA, we visited what you were involved in and I must say that Makerere has great potential. We received close to 102 proposals, and selecting seventeen (17) was a huge task because every proposition was bankable and attuned to the relevance of our country” Prof. Kakumba remarked.

The DVCAA noted that all projects undertaken by fellows had the potential to co-create knowledge with the communities and respective sectors beyond SECA funding. He therefore called upon them to continue providing research leadership in their departments and communities. On this note, he appreciated the fellows for each mentoring a graduate student.

Prof. Kakumba equally acknowledged CCNY for the generous support accorded to Makerere and continually entrusting the University with various opportunities to enhance the research capacities of her staff. In this regard, he thanked the Mentors, Heads of Department and the PIC for ensuring that the fellows continued to perform well and compile their progressive reports on time. This feat, he acknowledged, has led to Makerere University securing a successor grant in line with SECA.

Addressing the fellows and audience, Prof. Bbaale paid tribute to his predecessor, Prof. Buyinza for his visionary leadership of DRGT that gave rise to initiatives such as SECA. “It is gratifying and heartwarming to have events of this nature that are in line with the research-led agenda of the University.

The Deputy Director DRGT and the Workshop Moderator, Prof. Julius Kikooma contributes to the discussion.
The Deputy Director DRGT and the Workshop Moderator, Prof. Julius Kikooma contributes to the discussion.

“Postdoctoral research is high quality research, which can go a long way in informing policy for societal transformation. We greatly value each of the projects you have undertaken and we are confident that they have the potential to contribute to the national development agenda. Therefore, we must bring on board targeted dissemination beyond this general dissemination” said Prof. Bbaale.

He explained that targeted dissemination is the gateway to different institutions of Government that are either users or potential users of policy recommendations and different projects that need to be scaled up across the country. Beyond SECA, Prof. Bbaale urged the fellows to form a cluster of researchers as a platform for continued collaboration and a multidisciplinary entity to compete for research grants.

“The world over, postdoctoral research is an engine that must propel the university into a research-led direction… As DRGT, we are soon going to propose a policy on postdoctoral degrees that will pave the way for different units to admit many more postdoctoral fellows” added Prof. Bbaale.

Makerere’s strategic thinking in terms of research is informed by the Sustainable Development Goals (SDGs), National Vision 2040, African Charter 2063 and the Institutional Research Framework, which implies that we are running a coherent research agenda” said Prof. Buyinza as he commenced his remarks.

Dr. Kavuma Namirembe Susan from the Department of Policy and Development Economics, College of Business and Management Sciences (CoBAMS) presents her findings on the evaluation of Spatial Connectivity and Firm Productivity.
Dr. Kavuma Namirembe Susan from the Department of Policy and Development Economics, College of Business and Management Sciences (CoBAMS) presents her findings on the evaluation of Spatial Connectivity and Firm Productivity.

The Academic Registrar added that the realization of these aspirations is dependent on grooming a crop of critical thinkers who can contribute to the knowledge economy. He therefore expressed his gratitude at being able to participate in a number of phases of CCCNY’s support to Makerere, aimed at achieving this objective.

“I have been privileged to participate in the Next Generation of African Academics I, Next Generation of African Academics II, Nurturing Emerging Research Leaders through Post-Doctoral Training (NERLP) and Supporting Early-Career Academics (SECA), which we are closing today, and the successor consolidating the Supporting Early-Career Academics (SECA) programme” he explained.

Turning to SECA, Prof. Buyinza noted that the project was designed to expand Makerere’s community of research leaders and doctoral supervisors through four (4) specific objectives. These included;

  1. To consolidate the capacity of fellows to conduct quality research with appropriate mentorship at Makerere,
  2. To strengthen the enabling environment to encourage the retention of fellows at Makerere,
  3. To strengthen research management and research leadership capacity at Makerere, and
  4. To increase the capacity for scientific communication of research outputs into publicly accessible writing.

“We believe that we have built an integrated, institutionalized, research mentorship culture at this University because of our model of delivery of this project. It is a three-tier model consisting of the Senior who is the Mentor, the PI (Principal Investigator) who is the Early-Career fellow and the Masters student” said Prof. Buyinza.

Dr. Andrew Tamale from the Department of Wildlife and Aquatic Animal Resources, College of Veterinary Medicine, Animal Resources and Biosecurity (CoVAB) presents his findings on Management of Bacterial Diseases in Fish Hatcheries.
Dr. Andrew Tamale from the Department of Wildlife and Aquatic Animal Resources, College of Veterinary Medicine, Animal Resources and Biosecurity (CoVAB) presents his findings on Management of Bacterial Diseases in Fish Hatcheries.

He added that this architecture enabled the SECA team to build synergies between the different levels of research development and in so doing, ensure sustainability by institutionalizing mentorship. Prof. Buyinza therefore encouraged the fellows to continue posting their successes on the SECA portal and holding the lunchtime seminars in their departments.

“I want to believe that your skills have been enhanced, your vision to research has been touched beyond publishing an article to looking at the wider spectra of events that form you as a regional research leader. We want you to form a regional network so that together you can write research grants, supervise graduate students and influence the research agenda in the different countries” concluded Prof. Buyinza.

Details of the fellows and their research projects may be viewed in the table below.

No.NameUnitProject Title
1.Dr. Dhabangi AggreyChild Health and Development Centre (CHDC), CHS.Hemolytic Disease of the New-born in Uganda: Burden and Clinical Characteristics
2.Dr. Edopu Nabuyungo RitahDepartment of Fine Art, MTSIFA, CEDAT.Community Product Design Education for Improved Market Access.
3.Dr. Kabagenyi AllenDepartment of Population Studies, CoBAMS.Adolescent Motherhood, pre and postnatal New-born care practices, perceptions and barriers in Eastern Uganda (AMNEP).
4.Dr. Kambugu RobertDepartment of Agricultural and Biosystems Engineering, CAESModeling of long-term development scenarios for plantation forestry and forest industries in Uganda.
5.Dr. Kavuma Namirembe SusanDepartment of Policy and Development Economics, CoBAMSEmpirical Evaluation of Spatial Connectivity, Urban structure, Density and Firm Productivity: Evidence from Kampala.
6.Dr. Kindi Immanuel FredrickSchool of Women and Gender Studies, CHUSS.Gender, Oil and Migration in the Albertine Graben Region, Uganda.
7.Dr. Mayanja Nanziri MaureenDepartment of Bio-security, Ecosystem and Veterinary Public Health, CoVAB.Ethnoveterinary Medicinal Plant Technology Information Pathways and Prospective for Sustained Usage among Transhumant Pastrolists in Karamoja.
8.Dr. Muhanguzi DenisDepartment of Bio-molecular and Bio-Laboratory Sciences, CoVABTargeting hotspot villages to accelerate the eradication of Acute Sleeping Sickness (ASS) from Uganda.
9.Dr. Mwesigye Rutabatiina AbrahamDepartment of Forestry, Biodiversity and Tourism, CAES.Epidemiological survey of populations exposed to heavy metals and trace elements from Mining activites in Uganda. A case study of Kilembe copper mine catchment.
10.Dr. Mwikirize CosmasDepartment of Electrical and Computer Engineering, School of Engineering, CEDAT.Efficacy of Deep Learning-aided Platform for Diagnosis of Breast Cancer using Ultrasound Images in the Ugandan Population.
11.Dr. Najjemba Harriet P.Institute of Open Distance and E-learning, CEES.Using Emerging Technologies to Capture and Disseminate Indigenous Agricultural Practices for Improved Food Production in Uganda: A case of Luweero District (INDIGRIC).
12.Dr. Nambi RebeccaDepartment of Humanities and Language Education, CEES.Supporting refugee access and participation in higher education: A case of Makerere University.
13.Dr. Nasirumbi B. LosiraSchool of Agricultural Sciences, CAES.Intra-household gender dynamics and uptake of agricultural technologies for sustainable livelihoods in Uganda.
14.Dr. Semujju BrianDepartment of Journalism and Communication, CHUSS.Evaluating Digital Literacy to Create a Policy for Digital Media use at Makerere University.
15.Dr. Ssekuubwa EnockDepartment of Forestry, Biodiversity and Tourism, CAES.Enhancing the use of Farmer-Managed Natural Regeneration for mitigating climate change, conserving biodiversity and improving livelihoods in Uganda’s Cattle Corridor (FMNR).
16.Dr. Tamale AndrewDepartment of Wildlife and Aquatic Animal Resources, CoVAB.Operationalization of Phages for Management of Bacterial Diseases in Fish Hatcheries
17.Dr. Zawedde AminahMinistry of ICT and National Guidance. Formerly CoCIS.QATE: A Public Participatory Approach for Quality Assessment of e-Government Services to Enable Sustainable Development.
SECA Project Postdoctoral Research Teams (2019-2022)

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Health

Impact Program PhD Fellowships (Cohort 2): Deadline Extended

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The Director, Research and Graduate Training (DRGT), Prof. Buyinza Mukadasi (Centre black cap) poses with some of the PhD Graduands from CHS, CoNAS and the School of Law during the First Session of Makerere University's 72nd Graduation Ceremony on 23rd May 2022.

Makerere University in collaboration with the Uganda Heart Institute, Cincinnati Children’s Hospital Medical Center and Children’s National Hospital received funding from the National Institutes of Health’s Fogarty International Centre to implement the Impact Training Program. The goal of the program is to equip and nurture emerging research leaders and
professional scholars in Uganda to generate high-quality contemporary evidence on rheumatic heart disease (RHD) across the lifespan and to create an enduring research training center on the African continent that will rapidly advance progress towards the elimination of the disease in a generation. The impact program is soliciting for applications for Cohort 2, 4-year PhD scholarships tenable at Makerere University.

Eligibility

  1. Must be junior or mid-level researcher/scientist affiliated to Makerere University and Uganda Heart Institute.
  2. Prior master’s degree or fellowship in medicine, social sciences, gender studies or biomedical/health related field.
  3. Able to articulate a clear research RHD problem.
  4. Demonstrate interest in RHD research and commitment to develop a productive career in RHD research.
  5. Demonstrate a basic understanding of RHD in order to know that this is an appropriate next step for the applicant.
  6. Willingness to undertake and complete all training as mandated by the Impact program
  7. Commitment to publish research conducted under this training in open access peer reviewed journals.

Please see Downloads for detailed selection criteria and application process.

Closing date for the receipt of applications is January 20, 2023.

Enquiries can be forwarded to the Impact Program Coordinator, 1st Floor Clinical Research Building, Room 1.4, makimpact22@gmail.com.

Successful candidates must complete training in responsible conduct of research (RCR), protection of human research participants (PHRP) and good clinical practice (GCP) before they conduct research involving human research subjects.

Timelines:

Application deadline: January 20, 2023
Interviews: February 13-17, 2023
Notification date: February 24, 2023

Applicants should demonstrate excellent communications skills and will be expected to work as part of a highly motivated, result oriented RHD group.

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